array:24 [ "pii" => "S2173573512000476" "issn" => "21735735" "doi" => "10.1016/j.otoeng.2011.02.005" "estado" => "S300" "fechaPublicacion" => "2012-05-01" "aid" => "277" "copyright" => "Elsevier España, S.L.. All rights reserved" "copyrightAnyo" => "2011" "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Acta Otorrinolaringol Esp. 2012;63:218-29" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3001 "formatos" => array:3 [ "EPUB" => 55 "HTML" => 2094 "PDF" => 852 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001651911000549" "issn" => "00016519" "doi" => "10.1016/j.otorri.2011.02.006" "estado" => "S300" "fechaPublicacion" => "2012-05-01" "aid" => "277" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "ssu" "cita" => "Acta Otorrinolaringol Esp. 2012;63:218-29" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 19327 "formatos" => array:3 [ "EPUB" => 63 "HTML" => 17491 "PDF" => 1773 ] ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Hipoacusias hereditarias: asesoramiento genético" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "218" "paginaFinal" => "229" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Hereditary hearing loss: genetic counselling" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rubén Cabanillas Farpón, Juan Cadiñanos Bañales" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Rubén" "apellidos" => "Cabanillas Farpón" ] 1 => array:2 [ "nombre" => "Juan" "apellidos" => "Cadiñanos Bañales" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173573512000476" "doi" => "10.1016/j.otoeng.2011.02.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573512000476?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001651911000549?idApp=UINPBA00004N" "url" => "/00016519/0000006300000003/v1_201304231449/S0001651911000549/v1_201304231449/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173573512000567" "issn" => "21735735" "doi" => "10.1016/j.otoeng.2010.11.006" "estado" => "S300" "fechaPublicacion" => "2012-05-01" "aid" => "248" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Acta Otorrinolaringol Esp. 2012;63:230-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2718 "formatos" => array:3 [ "EPUB" => 57 "HTML" => 1957 "PDF" => 704 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case study</span>" "titulo" => "Laryngeal Sarcoidosis: Unique Location or First Manifestation?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "230" "paginaFinal" => "232" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Sarcoidosis laríngea: ¿localización única o primera manifestación?" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 956 "Ancho" => 993 "Tamanyo" => 148577 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Laryngoscopy (after reactivation of symptoms): tumour mass on right arytenoepiglottic fold and ventricular band.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ángel Lede Barreiro, Juan J. Díaz Argüello, José A. Fernández Martínez, Alfonso Martínez Ferreras" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Ángel" "apellidos" => "Lede Barreiro" ] 1 => array:2 [ "nombre" => "Juan J." "apellidos" => "Díaz Argüello" ] 2 => array:2 [ "nombre" => "José A." "apellidos" => "Fernández Martínez" ] 3 => array:2 [ "nombre" => "Alfonso" "apellidos" => "Martínez Ferreras" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001651910002074" "doi" => "10.1016/j.otorri.2010.11.015" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001651910002074?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573512000567?idApp=UINPBA00004N" "url" => "/21735735/0000006300000003/v1_201304231514/S2173573512000567/v1_201304231514/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173573512000531" "issn" => "21735735" "doi" => "10.1016/j.otoeng.2012.01.013" "estado" => "S300" "fechaPublicacion" => "2012-05-01" "aid" => "347" "copyright" => "Elsevier España, S.L." "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Acta Otorrinolaringol Esp. 2012;63:212-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2979 "formatos" => array:3 [ "EPUB" => 60 "HTML" => 2081 "PDF" => 838 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Peritonsillar Infections: Prospective Study of 100 Consecutive Cases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "212" "paginaFinal" => "217" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Infecciones periamigdalinas: estudio prospectivo de 100 casos consecutivos" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "María Costales-Marcos, Fernando López-Álvarez, Faustino Núñez-Batalla, Carla Moreno-Galindo, César Álvarez Marcos, José Luis Llorente-Pendás" "autores" => array:6 [ 0 => array:2 [ "nombre" => "María" "apellidos" => "Costales-Marcos" ] 1 => array:2 [ "nombre" => "Fernando" "apellidos" => "López-Álvarez" ] 2 => array:2 [ "nombre" => "Faustino" "apellidos" => "Núñez-Batalla" ] 3 => array:2 [ "nombre" => "Carla" "apellidos" => "Moreno-Galindo" ] 4 => array:2 [ "nombre" => "César" "apellidos" => "Álvarez Marcos" ] 5 => array:2 [ "nombre" => "José Luis" "apellidos" => "Llorente-Pendás" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001651912000143" "doi" => "10.1016/j.otorri.2012.01.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001651912000143?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573512000531?idApp=UINPBA00004N" "url" => "/21735735/0000006300000003/v1_201304231514/S2173573512000531/v1_201304231514/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>" "titulo" => "Hereditary Hearing Loss: Genetic Counselling" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "218" "paginaFinal" => "229" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Rubén Cabanillas Farpón, Juan Cadiñanos Bañales" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Rubén" "apellidos" => "Cabanillas Farpón" "email" => array:1 [ 0 => "rcabanillas@imoma.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Juan" "apellidos" => "Cadiñanos Bañales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Unidad de Oncología Clínica y Traslacional, Instituto de Medicina Oncológica y Molecular de Asturias, Oviedo, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Laboratorio de Medicina Molecular, Instituto de Medicina Oncológica y Molecular de Asturias, Oviedo, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipoacusias hereditarias: asesoramiento genético" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">It is estimated that at least 60% of early-onset hearing loss or hypoacusis cases respond to a genetic cause, whilst the remaining 40% are attributed to environmental causes. The latter include prenatal infections (cytomegalovirus, herpesvirus, rubella, toxoplasma, etc.), postnatal infections (bacterial meningitis), foetal distress, hyperbilirubinemia or ototoxic drugs.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> These percentages have been changing in recent years in parallel with the technological development experienced by molecular biology. It is important to note that the presence of an environmental cause does not necessarily exclude the existence of an underlying genetic predisposition. The genetic analysis of patients with hearing loss due to environmental causes commonly identifies pathogenic mutations.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> This is true both in early-onset and late-onset hearing losses, where the interaction between environmental and genetic factors is even more complex.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> Therefore, caution is required when classifying hearing loss as environmental, since this may have important implications at the time of genetic counselling (for example, probability of occurrence of new cases in the family).</p><p id="par0010" class="elsevierStylePara elsevierViewall">Genetic or hereditary hearing loss can be classified as conductive, perceptive or mixed; as syndromic or non-syndromic; and finally, as pre-lingual or post-lingual. Hearing loss is labelled as syndromic when associated with external ear malformations or manifestations in other organs or systems. By contrast, non-syndromic cases are not associated with other medical problems, although they may present abnormalities in the middle or inner ear. Approximately 30% of pre-lingual genetic hearing loss cases are syndromic (hypoacusis is an identifiable symptom in over 400 different syndromes<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>). In the remaining 70% of cases, hearing loss is not associated with any other clinical manifestations (non-syndromic hearing loss). Among pre-lingual non-syndromic hearing loss cases, 80% are inherited following an autosomal recessive (AR) pattern, 18% follow an autosomal dominant (AD) pattern and the remaining 2% correspond to hearing loss with X-linked and mitochondrial genome inheritance.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The percentages for each inheritance pattern in cases of post-lingual non-syndromic hearing loss are currently unknown. However, the percentage of families with an AD pattern is higher than the pre-lingual.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In order to classify non-syndromic hearing loss, the different loci (chromosomal regions where those genes associated with the disease are located) are designated as DFN (derived from DeaFNess), followed by a number related to the chronological order of their discovery. AD loci are known as DFNA, AR loci are known as DFNB and X-linked loci are known as DNFX.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Genetic Characteristics of Hereditary Hypoacusis</span><p id="par0020" class="elsevierStylePara elsevierViewall">When designing the study of hereditary hearing loss it is essential to be familiar with four classical genetic concepts which characterise them:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0025" class="elsevierStylePara elsevierViewall">Incomplete penetrance: only a certain percentage of individuals carrying the altered gene manifest the disease. For example, only 60% of individuals carrying a heterozygous mutation in the <span class="elsevierStyleItalic">PAX3</span> gene (Waardenburg syndrome type 1 and type 3) develop hearing loss.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">Variable expressivity: the severity of clinical manifestations differs between individuals carrying the same mutation. For example, individuals carrying a heterozygous mutation in the <span class="elsevierStyleItalic">WFS1</span> gene may present moderate perceptive post-lingual hearing loss as the only symptom<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> or else present other characteristic symptoms of Wolfram syndrome (diabetes mellitus and/or optic atrophy).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">Genetic heterogeneity: mutations in different genes can cause the same clinical manifestation. In fact, there are at least 30 genes capable of causing pre-lingual non-syndromic hearing loss with an autosomal recessive pattern (<span class="elsevierStyleItalic">GJB2</span>, <span class="elsevierStyleItalic">GJB6</span>, <span class="elsevierStyleItalic">OTOF</span>, <span class="elsevierStyleItalic">TECTA</span>, <span class="elsevierStyleItalic">MYO7A</span>, etc.).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Allelic heterogeneity: a single mutation can give rise to different diseases. For example, the recurrent mutation 35delG in the <span class="elsevierStyleItalic">GJB2</span> gene (connexin 26), can cause AR non-syndromic hearing loss (DFNB1), AD non-syndromic hearing loss (DFNA3) or a syndrome with cutaneous, vascular or thyroid manifestations.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">Therefore, in the case of genetic hearing loss, incomplete penetrance, variable expressivity and genetic and allelic heterogeneity hinder the establishment of correlations between a specific mutation (genotype) and its clinical and audiometric manifestations (phenotype). This partly justifies the difficulty of integrating genetic counselling in daily clinical practice, despite its benefits for patients and their families.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Genetic Counselling</span><p id="par0050" class="elsevierStylePara elsevierViewall">Genetic advice or counselling is defined as a communication process in which patients and/or their families are informed of the likelihood of developing a particular, genetically determined disease, the risk of transmitting it, its preventive measures, early diagnosis, and available treatment, as well as the possibility of conducting a genetic study, which is not always feasible or necessary.</p><p id="par0055" class="elsevierStylePara elsevierViewall">During genetic counselling, it is important to note that some deaf people do not consider hearing loss as a ‘deficit’ and do not wish for their deafness to be considered as a disease to be treated or cured. Moreover, some deaf couples wish to have deaf children. Therefore, although the process of genetic counselling should always place its emphasis on respecting patient individuality and not being directive, these assumptions are particularly important in the case of deaf patients. It is also necessary to consider that hearing loss and its possible associated communication difficulties may represent a problem at the time of counselling.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Genetic studies in Spain are regulated by the Biosanitary Research Act 14/2007. This law establishes the need for a process of genetic counselling before and after the completion of any genetic test, as well as the need for specific informed consent. Therefore, the results of a genetic test must always be presented within an environment of genetic counselling. In this consultation, patients and their families should be informed about the ethical and social issues associated with genetic studies (confidentiality, implications for family, risk of social and labour discrimination, possibility of revealing false paternity, attitude with uncertain results, psychological implications, etc.).<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Therefore, if following an appropriate clinical diagnosis there is suspicion that hearing loss could have a hereditary origin, patients should be referred to genetic counselling. This specialist consultation should be part of the multidisciplinary team responsible for managing deaf patients. It should integrate otolaryngologists, speech therapists, paediatricians, phoniatricians, clinical geneticists and, eventually, neurologists and ophthalmologists.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> This consultation, prior to discussion with the patient and/or their families about the possibility of conducting a genetic study, should attempt to characterise hearing loss as far as possible.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Aetiological Diagnosis of Sensorineural Hearing Loss</span><p id="par0070" class="elsevierStylePara elsevierViewall">The aetiological diagnosis of a potentially genetic sensorineural hearing loss is complex and there is no standardised protocol for it.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,16</span></a> Furthermore, we must not forget that the boundary between environmental and genetic hearing loss is becoming increasingly difficult to establish. Examples of this are the identification of mutations in the <span class="elsevierStyleItalic">GJB2</span> gene in allegedly environmental cases<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3</span></a> or in the <span class="elsevierStyleItalic">OTOF</span> gene in apparently sporadic cases (with no family history).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In order to obtain an aetiological diagnosis it is necessary to accurately know the family and personal history, conduct a thorough physical examination and, when indicated, request additional radiological, biochemical or genetic studies. A correct coordination between the different members of the multidisciplinary team will avoid unnecessary duplication of diagnostic tests.</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Family History</span><p id="par0080" class="elsevierStylePara elsevierViewall">Building a good family tree is the starting point for adequate genetic counselling. Ideally, it should cover three generations and include, at least, audiological and otological examinations of first-degree relatives of the index case. Incomplete penetrance, variable expressivity and genetic and allelic heterogeneity should be taken into account when assessing a family tree, especially for genetic counselling of family members. It is important to remember that family history is dynamic, and therefore should be reassessed in subsequent reviews. The evaluation of a specific genealogy should always take into account the possibility of false paternities, adoptions or even the possibility of mutations arising de novo, establishing patients as first carriers in the family.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> The identification of a transmission pattern within a family represents a significant step for genetic counselling.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Personal History</span><p id="par0085" class="elsevierStylePara elsevierViewall">A detailed medical history should include information on maternal health, pregnancy, childbirth and the postnatal period. Special attention should be paid to the use of potentially ototoxic drugs during pregnancy, including alcohol consumption. Infections should also be considered, especially bacterial meningitis. It is necessary to rule out disease in other organs or systems, especially neurological, ophthalmological or vestibular. Furthermore, in children it is important to note an adequate progression through various psychomotor development milestones.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Physical Examination</span><p id="par0090" class="elsevierStylePara elsevierViewall">The first goal should be to classify hearing loss as syndromic or non-syndromic. This requires a thorough and systematic exploration, with attention to the characteristic signs of the most common syndromes (for example, auricular malformations, branchial cysts, white forelock, telecanthus, goitre, craniofacial and skeletal abnormalities, etc.).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Complementary Studies</span><p id="par0095" class="elsevierStylePara elsevierViewall">After an adequate auditive assessment (otoacoustic emissions, auditory evoked potentials, tympanometry, acoustic stapedial reflex and age-appropriate audiometry), the type of hearing loss and age of the patient should guide which tests to be requested. Possible studies to be considered include magnetic resonance imaging (MRI) and computed tomography (CT) scans, renal ultrasound, serologies (cytomegalovirus, toxoplasmosis, syphilis, rubella, etc.), blood and urine biochemical analyses, electrocardiogram, eye fundus and electroretinography.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Except for MRI and CT scans, the diagnostic usefulness of the other tests in previously unscreened patients is very low and their role in diagnostic protocols has not been adequately defined.<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,20,21</span></a> However, we must not forget that they can be highly relevant in certain cases, such as detection of abnormalities in the electrocardiogram of patients with Jervell and Lange-Nielsen syndromes, hypothyroidism in a percentage of patients with Prendred syndrome, renal failure in Alström, Alport and branchio-oto-renal syndromes, etc.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Inner ear MRI and temporal bone CT scans enable detection of inner ear malformations. As we shall see, some of these are correlated with the presence of mutations in certain genes (for example, Mondini aplasia, enlarged vestibular aqueduct, dilation of the internal auditory canal, etc.). However, the genetic heterogeneity typical of hearing loss limits their usefulness (for example, enlarged vestibular aqueduct, considered as a classic sign of mutations in the SLC26A4 gene,<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> can be found relatively frequently in patients with mutations in the GJB2 gene<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>).</p><p id="par0110" class="elsevierStylePara elsevierViewall">Currently, in children, genetic studies must always be the first step in the aetiological diagnosis of moderate to severe sensorineural non-syndromic hearing loss,<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14–16,26</span></a> except in specific cases where the probability of finding a radiological anomaly is relatively high (mild hearing loss, late-onset, progressive or fluctuating hearing loss and hearing loss with associated vestibular or craniofacial pathology).<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,25</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Genetic Studies</span><p id="par0115" class="elsevierStylePara elsevierViewall">Whenever it is not possible to identify a clear cause through medical history or physical examination, genetic studies represent the diagnostic test with the highest performance in non-syndromic sensorineural hearing loss in both children<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16,26,27</span></a> and adults.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Moreover, conducting these studies in young children is very simple (they only require a sample of blood or saliva). Therefore, genetic counselling should be a fundamental pillar in the diagnosis of sensorineural hearing loss.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Usefulness of Genetic Diagnosis</span><p id="par0120" class="elsevierStylePara elsevierViewall">Identifying the presence of a genetic predisposition within a family has multiple advantages for both healthy individuals and those who have already manifested the disease. It is very important to note that different families and individuals expect to obtain different information from genetic counselling. In some cases their interest is mainly focused on reproductive and family planning issues. In others, their interest is to know the cause of their deafness and its medical and social implications. Therefore, objectives should always be oriented towards the concerns of patients and their families.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">The benefits for family members may include the possibility of detecting carriers who are currently asymptomatic, assessing the risk of transmission to offspring and avoiding uncertainty, anxiety and unnecessary testing of non-carriers.</p><p id="par0130" class="elsevierStylePara elsevierViewall">The benefits for patients can be classified into five main areas: prevention, diagnosis, prognosis, treatment and reproduction.<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">Prevention: preventive measures are effective in hereditary hearing loss conditioned by environmental factors, such as mutations conferring sensitivity to aminoglycosides<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> or cisplatin toxicity.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Often, deafness may be the first manifestation of a more complex syndrome. Therefore, when the mutation identified may cause syndromic manifestations, it is essential to contemplate the potential involvement of other organs, even if this is not present at the time of diagnosis (loss of vision, cardiac conduction defects, kidney failure, etc.).</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0140" class="elsevierStylePara elsevierViewall">Diagnosis: knowing the cause of deafness can often help patients or their parents to emotionally assimilate diagnosis, accelerating their involvement in rehabilitation treatment. In addition, a genetic diagnosis can prevent unnecessary testing (CT, MRI, neurophysiological studies, etc.).</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0145" class="elsevierStylePara elsevierViewall">Prognosis: it is often possible to predict the evolution of deafness, establishing a prognosis based on the genotype of each patient.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a> In this case, genetic studies condition the monitoring protocol, hearing rehabilitation plan and educational decisions (rapidly progressive hearing loss affecting all frequencies versus stable hearing loss involving only a specific range of frequencies).</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0150" class="elsevierStylePara elsevierViewall">Treatment: knowing the cause of deafness may be useful when making treatment decisions. For example, patients with hearing loss secondary to mutations in the <span class="elsevierStyleItalic">GJB2</span> and <span class="elsevierStyleItalic">GJB6</span> genes obtain more benefit from cochlear implants than patients with hereditary hearing loss without mutations in these genes, with the results of implantation usually being excellent.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32,33</span></a> Patients with hereditary hearing loss with predominance in high and middle tones who are stable over time (for example, certain mutations in the <span class="elsevierStyleItalic">TECTA</span> gene) may be good candidates for shorter cochlear implants, supported by hearing aids.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> On the other hand, hearing loss and vestibular symptoms caused by mutations in the <span class="elsevierStyleItalic">COCH</span> gene, have occasionally been associated with superior semicircular canal dehiscence,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> in which case surgical improvement of symptoms is a possibility.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> On the other hand, the correct treatment of neuropathies requires knowledge of their aetiology, discriminating between different genetic and environmental causes. Thus, for example, auditory neuropathy secondary to mutations in the <span class="elsevierStyleItalic">OTOF</span> gene does not affect auditory nerve function (see specific section). Therefore, cochlear implants usually provide a good performance in these patients.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> However, specific mutations in the <span class="elsevierStyleItalic">PJVK</span> gene can induce primary neural dysfunction<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> and, therefore, compromise the results of potential cochlear implantation in patients with a similar audiometric profile to that observable with mutations in the <span class="elsevierStyleItalic">OTOF</span> gene.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0155" class="elsevierStylePara elsevierViewall">Reproduction: after identifying a gene and its inheritance pattern it is possible to accurately determine the probability of having deaf children. Thus, for example, two parents affected by AR inheritance hearing loss will have deaf descendants in 100% of cases if their mutations are in the same gene. Conversely, if the mutations affect different genes, none of their children will inherit the disorder. Identification of the mutation responsible will enable discussion of the available reproductive options, as well as the associated legal and ethical considerations (preimplantation genetic diagnosis, prenatal genetic diagnosis). It may also be possible to determine the presence or absence of the mutation in the newborn, thus speeding the diagnostic and therapeutic processes. In those cases where it is not possible to identify the gene responsible or to establish an inheritance pattern, it may possible to use empirical percentages in the counselling process. Thus, for example, a priori, when a couple with normal hearing and no family history of hearing loss have a deaf child, their chance of having another deaf child is 18%. The probability that a couple formed by one deaf individual and one with normal hearing have a deaf child is 10%. If a genetic study has been performed and has found no pathogenic mutations these figures may be modified, depending on the genes analysed.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">In addition to the usefulness for patients and their families, we must also bear in mind the importance of genetic studies to advance the knowledge of inherited hearing disorders. Including patients in homogeneous aetiological groups helps to further the genotype–phenotype correlation and helps to establish the efficacy of various therapeutic measures in these different groups. Moreover, knowing the prevalence of different mutations within our population increases the efficiency of genetic studies. In the future, a deeper understanding of the pathophysiological mechanism responsible for a particular type of hearing loss could enable specific therapies directed against specific molecular alterations.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Non-syndromic Genetic Hearing Loss: Genes Most Frequently Involved</span><p id="par0165" class="elsevierStylePara elsevierViewall">Most of the genes responsible for non-syndromic genetic hearing loss encode proteins involved in the development, structure and function of the cochlea. <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1–3</a> list the over 50 genes identified so far.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> We should note that, due to the allelic and genetic heterogeneity described previously, a single gene may appear in more than one table. Moreover, some of these genes are also responsible for syndromic hearing loss.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">As a general rule, we can say that the majority of recessive hearing losses (DFNB) cause a moderate to deep pre-lingual deafness, which is stable over time. By contrast, dominant hearing losses (DFNA) are usually post-lingual and progressive. Those linked to the X chromosome (DFNX) may be both pre-lingual and post-lingual. However, there are numerous exceptions to this rule. Mutations in genes such as <span class="elsevierStyleItalic">TMPRSS3</span> (DFNB8/DFNB10), <span class="elsevierStyleItalic">MYO3A</span> (DFNB30), <span class="elsevierStyleItalic">PJVK</span> (DFNB59), <span class="elsevierStyleItalic">LOXHD1</span> (DFNB77) or <span class="elsevierStyleItalic">TPRN</span> (DFNB79) may lead to progressive hearing loss with AR inheritance.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">42,43</span></a> In these cases, when hearing loss begins in the third or fourth decade of life it could be mistaken for sporadic or environmentally caused hearing loss, given the progressive nature and inheritance pattern. By contrast, carriers of certain heterozygous mutations (AD inheritance) may develop early-onset profound hearing loss (for example, mutations in <span class="elsevierStyleItalic">GJB6</span> -DFNA3- or <span class="elsevierStyleItalic">TECTA</span> -DFNA8/DFNA12-).</p><p id="par0175" class="elsevierStylePara elsevierViewall">Next, we will carry out a brief description of those genes whose mutations are identified most frequently in our environment.</p><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Connexins</span><p id="par0180" class="elsevierStylePara elsevierViewall">Connexins are a family of proteins responsible for the formation of intercellular channels. When these channels are grouped they originate so-called gap junctions. These channels enable the gradient-wise flow of ions and metabolites between adjacent cells. Each channel is formed by two hemichannels or connexons. In turn, each connexon is composed of six connexin molecules. Gap junctions in the cochlea are formed by four types of connexins: connexin (Cx) 26 (<span class="elsevierStyleItalic">GJB2</span> gene), Cx30 (<span class="elsevierStyleItalic">GJB6</span> gene), CX31 (<span class="elsevierStyleItalic">GJB3</span> gene) and Cx43 (<span class="elsevierStyleItalic">GJA1</span> gene). Their correct function is necessary for the maintenance of ionic and metabolic cochlear homeostasis. Their alteration would result in the onset of hearing loss through various mechanisms (altered potassium flows, impairment of the endothelial barrier in the stria vascularis, etc.).<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Mutations in the <span class="elsevierStyleItalic">GJB2</span>, <span class="elsevierStyleItalic">GJB6</span> and <span class="elsevierStyleItalic">GJB3</span> genes together represent the most common cause of hereditary non-syndromic hearing loss in our environment. Mutations in the <span class="elsevierStyleItalic">GJA1</span> gene cause different syndromes which be associated with conductive hearing loss (oculodentodigital dysplasia, Hallermann-Streiff syndrome or hypoplastic left heart syndrome).<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">GJB2</span></span><p id="par0185" class="elsevierStylePara elsevierViewall">Its mutations are the most common cause of non-syndromic hearing loss with AR inheritance (DFNB1A).<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> To date, over 100 pathogenic mutations have been identified in this gene.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However, the 35delG mutation is responsible for most mutant alleles in populations of European origin. The high prevalence of these mutations (up to 3% of the Caucasian population can be carriers<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>) and the existence of a recurrent mutation have made the study of this gene part of the routine molecular diagnosis of most laboratories.</p><p id="par0190" class="elsevierStylePara elsevierViewall">Patients carrying a homozygous mutation in <span class="elsevierStyleItalic">GJB2</span> usually suffer severe early-onset hearing loss. However, although the phenotype is usually homogeneous, the <span class="elsevierStyleItalic">GJB2</span> gene is a good example of allelic heterogeneity.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> On the one hand, it has been possible to observe every degree of hearing impairment (moderate to profound), and even asymmetric hearing loss, in patients with homozygous mutations.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,31</span></a> On the other hand, mutations in <span class="elsevierStyleItalic">GJB2</span> may be responsible for both non-syndromic hearing loss with autosomal dominant inheritance (DFNA3A) and for different syndromes with more or less severe phenotypes. The latter may range from changes in skin pigmentation<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> to mutilating keratoderma (Vohwinkel syndrome).<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> There have been attempts at establishing a genotype–phenotype relationship in which the severity of the deficit is correlated with the specific type of mutation, obtaining conclusive results in studies with a sufficient number of patients.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Among populations with a European origin it is not uncommon to encounter patients with one heterozygous mutation in <span class="elsevierStyleItalic">GJB2</span> and another, also heterozygous, in <span class="elsevierStyleItalic">GJB6</span>. These patients are known as compound heterozygotes.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">GJB6</span></span><p id="par0200" class="elsevierStylePara elsevierViewall">Mutations in this gene are the second cause of pre-lingual hereditary hearing loss in the Spanish population, following the 35delG mutation of <span class="elsevierStyleItalic">GJB2</span>.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> They usually cause non-syndromic hearing loss with AR inheritance (DFB1B), with patients being either homozygotes or compound heterozygotes (one mutation in <span class="elsevierStyleItalic">GJB2</span> and another in <span class="elsevierStyleItalic">GJB6</span>).<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a> However, this gene is also responsible for AD non-syndromic (DFNA3B)<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> or syndromic (Clouston syndrome)<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> hearing losses. Overall, mutations in <span class="elsevierStyleItalic">GJB2</span> and <span class="elsevierStyleItalic">GJB6</span> are responsible for approximately 50% of non-syndromic hearing losses with AR inheritance (DFNB1).<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">GJB3</span></span><p id="par0205" class="elsevierStylePara elsevierViewall">As is also the case with other cochlear connexins, mutations in the <span class="elsevierStyleItalic">GJB3</span> gene can result in non-syndromic hearing loss with both AR and AD inheritance (DFNA2B)<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> or in syndromic cases with cutaneous<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a> or neurological<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> manifestations. As occurred with <span class="elsevierStyleItalic">GJB6</span> there have been recent reports of compound heterozygous patients, carriers of mutations in both <span class="elsevierStyleItalic">GJB2</span> and <span class="elsevierStyleItalic">GJB3</span>.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">OTOF</span></span><p id="par0210" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">OTOF</span> gene encodes the protein otoferlin, which is necessary for the proper functioning of the synapses between inner ciliated cells and underlying neurons (type I fibres of the cochlear nerve).<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> Their mutations usually result in AR non-syndromic hearing loss, with a specific and homogeneous phenotype (DFNB9). Homozygous individuals present pre-lingual profound hearing loss with preservation of otoacoustic emissions and absence of brainstem auditory evoked potentials (auditory neuropathy). Since the auditory nerve works correctly, cochlear implants in patients with mutations in the <span class="elsevierStyleItalic">OTOF</span> gene offer a similar performance to that obtained in other cochlear hearing losses.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> A recurrent mutation in this gene (Q829X) has been identified in Spain and among Hispanic populations. In Spain, this mutation is the third leading cause of genetic pre-lingual deafness, after connexin mutations.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,50,59</span></a> It is worth noting that certain mutations of this gene in heterozygosis may give rise to an intermittent hearing loss, precipitated by increased temperature (for example, fever episodes).<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">COCH</span></span><p id="par0215" class="elsevierStylePara elsevierViewall">Mutations in this gene are the most common cause of AD non-syndromic hearing loss (DFNA9). Its heterozygous mutations cause progressive late-onset hearing loss, with predominance in high frequencies, usually associated with vestibular dysfunction.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> When they appear, vestibular symptoms are similar to those of Meniere's disease (vertigo, tinnitus, aural fullness and hearing loss) and may precede auditory deterioration by up to 10 years.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> Therefore, its analysis should be considered in patients with suspected Meniere's disease and a family history, especially if hearing loss preferentially affects high tones.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">WFS1</span></span><p id="par0220" class="elsevierStylePara elsevierViewall">Heterozygous mutations of the <span class="elsevierStyleItalic">WFS1</span> gene may be asymptomatic or cause non-syndromic late-onset deafness, predominantly in low tones (DFNA6/DFNA14/DFNA38), pre-lingual hearing loss or even Wolfram syndrome.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy and deafness [DIDMOAD])<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a> is usually due to a homozygous mutation of <span class="elsevierStyleItalic">WFS1</span>. This syndrome is an example of genetic heterogeneity (it can also be caused by mutations in the <span class="elsevierStyleItalic">CISD2</span> gene)<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">62,63</span></a> with variable expressivity (manifestations may range from moderate hearing loss with predominance in high tones and type 2 diabetes to severe cases, with significant neurological deficits).<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">64,65</span></a> A recurrent mutation (425ins16) has been identified among the Spanish population, which is present in over 50% of families with Wolfram syndrome.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">MIRN96</span></span><p id="par0225" class="elsevierStylePara elsevierViewall">This gene does not encode a protein but a small fragment of RNA with a regulatory function (micro-RNA) expressed mainly in cochlear ciliated cells. Its mutations cause the development of hereditary non-syndromic hearing loss (DFNA50). These mutations are of particular interest in our environment, because they were initially described in the Spanish population and because they represent the first mutation responsible for deafness identified in micro-RNA.<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67,68</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle"><span class="elsevierStyleItalic">POU3F4</span></span><p id="par0230" class="elsevierStylePara elsevierViewall">This gene is located on the X chromosome and its mutations cause progressive early-onset hearing loss (DNFX2), which can be sensorineural or mixed (it may appear with stapes fixation). During stapedectomy, these patients are at risk of sudden and massive perilymph leakage (gusher). CT scans can identify a dilation of the internal auditory canal and dehiscence of its lateral wall.<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">69,70</span></a></p></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Mitochondrial Genes</span><p id="par0235" class="elsevierStylePara elsevierViewall">Generally, mutations in mitochondrial genes cause complex syndromes. However, certain mutations in genes such as <span class="elsevierStyleItalic">MTRNR1</span>, <span class="elsevierStyleItalic">MTTS1</span> or <span class="elsevierStyleItalic">MTTL1</span> may present hearing loss as their only symptom. In addition to their characteristic inheritance pattern, these disorders display high variability in terms of penetrance and severity. The most characteristic example is the 1555G→A mutation in the <span class="elsevierStyleItalic">MTRNR1</span> (<span class="elsevierStyleItalic">12srRNA</span>) gene. This mutation is considered as the most common cause of post-lingual hearing loss in the Spanish population.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28,50</span></a> In some individuals, hearing loss is triggered as a result of aminoglycoside antibiotics, while in others hearing loss appears spontaneously.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,71</span></a></p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Syndromic Genetic Hearing Loss: Most Common Syndromes</span><p id="par0240" class="elsevierStylePara elsevierViewall">As discussed, hearing loss is an identifiable symptom in over 400 different syndromes.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> However, in most syndromes hearing loss is mild or may even be absent. An adequate clinical evaluation within a multidisciplinary environment is essential to rule out syndromic hearing loss, since this diagnosis may have great relevance for the clinical management of patients (visual alterations, heart disease, kidney disease, etc.). As with non-syndromic hearing loss, in most syndromes the cause of deafness is located in the organ of Corti or the stria vascularis. However, in some cases dysfunction also affects neurons in the spiral ganglion, causing sensory and neural hearing loss, with subsequent diagnostic and therapeutic implications. A detailed analysis of the different syndromes is beyond the scope of this review, but the most common syndromes, as well as some of their most relevant clinical data, are described below, in order of frequency.</p><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Autosomal Recessive Inheritance</span><p id="par0245" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0250" class="elsevierStylePara elsevierViewall">Usher syndrome: pre-lingual sensorineural hearing loss and retinitis pigmentosa. The latter usually appears during the second decade of life. Patients are classified into three groups depending on the type of hearing loss, the presence or absence of vestibular involvement and the age of onset of retinitis. A total of nine genes responsible for this syndrome have been identified (<span class="elsevierStyleItalic">MYO7A</span>, <span class="elsevierStyleItalic">USH1C</span>, <span class="elsevierStyleItalic">CDH23</span>, <span class="elsevierStyleItalic">PCDH15</span>, <span class="elsevierStyleItalic">SANS</span>, <span class="elsevierStyleItalic">USH2A</span>, <span class="elsevierStyleItalic">VLGR1</span>, <span class="elsevierStyleItalic">WHRN</span>, and <span class="elsevierStyleItalic">USH3</span>).<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">72</span></a></p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0255" class="elsevierStylePara elsevierViewall">Pendred syndrome: sensory hearing loss, usually pre-lingual. The syndrome is characterised by the presence of goitre, which can develop either during puberty or in adulthood. Thyroid function is normal in over half of cases.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> Vestibular dysfunction and bone abnormalities in the inner ear are often present (Mondini dysplasia or dilated vestibular aqueduct). In 50% of cases it is possible to identify a mutation in the <span class="elsevierStyleItalic">SCL26A4</span> gene. The study of this gene would be indicated in patients with progressive hearing loss and radiological abnormalities of the bony labyrinth, regardless of the presence or absence of goitre (this gene is also responsible for DFNB4 non-syndromic hearing loss).<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a> Less frequently, Pendred syndrome may be caused by mutations in the <span class="elsevierStyleItalic">FOXI1</span> gene.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a></p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0260" class="elsevierStylePara elsevierViewall">Jervell and Lange-Nielsen syndrome: pre-lingual sensorineural hearing loss and prolonged QT interval. Affected patients are at risk for sudden death. Two responsible genes have been identified (<span class="elsevierStyleItalic">KCNE1</span> and <span class="elsevierStyleItalic">KCNQ1</span>).<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a></p></li></ul></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Autosomal Dominant Inheritance</span><p id="par0265" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0270" class="elsevierStylePara elsevierViewall">Waardenburg syndrome: sensorineural hearing loss of varying severity (mild or profound), unilateral or bilateral.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Associated abnormalities in skin, hair (characteristic white forelock) and eye (heterochromia iridis) pigmentation. Four types have been described and six genes have been identified (<span class="elsevierStyleItalic">PAX3</span>, <span class="elsevierStyleItalic">MITF</span>, <span class="elsevierStyleItalic">SNAI2</span>, <span class="elsevierStyleItalic">EDNRB</span>, <span class="elsevierStyleItalic">EDN3</span>, and <span class="elsevierStyleItalic">SOX10</span>).<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a></p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0275" class="elsevierStylePara elsevierViewall">Branchio-oto-renal syndrome: highly variable expressivity. Perceptive hearing loss, conductive or mixed, which may be associated with branchial cysts or fistulae, anomalies of the external ear canal and/or the ear, and kidney malformations. A total of three genes have been identified to date (<span class="elsevierStyleItalic">EYA1</span>, <span class="elsevierStyleItalic">SIX1</span>, and <span class="elsevierStyleItalic">SIX5</span>).<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">77,78</span></a></p></li></ul></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">X-linked Inheritance</span><p id="par0280" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">-</span><p id="par0285" class="elsevierStylePara elsevierViewall">Alport syndrome: post-lingual progressive hearing loss, associated with progressive glomerulonephritis. It often presents ocular abnormalities, with the most characteristic being anterior lenticonus. In 85% of cases, inheritance is linked to the X chromosome (<span class="elsevierStyleItalic">COL4A5</span> gene), but there have also been reports of autosomal forms (<span class="elsevierStyleItalic">COL4A3</span> and <span class="elsevierStyleItalic">COL4A4</span> genes), either AR, or occasionally AD.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">79</span></a></p></li></ul></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Mitochondrial Inheritance</span><p id="par0290" class="elsevierStylePara elsevierViewall">Generally, mitochondrial disorders are preferentially manifested in tissues with a high energy demand. Thus, mutations in the mitochondrial genome can cause many different syndromes, ranging from severe neuromuscular disorders (MERRF, MELAS, LHON, etc.) to milder and more common symptoms, such as diabetes mellitus type 2. Involvement of the auditory pathway is frequent in these syndromes with a mitochondrial origin. The common factor is the characteristic inheritance pattern (affecting both genders equally, only transmitted by the mother and affecting 100% of the offspring of an affected female). However, when evaluating a genealogy it is important to bear in mind the incomplete penetrance and variable expressivity of these syndromes. Among the genes identified so far we highlight <span class="elsevierStyleItalic">MTTL1</span>, <span class="elsevierStyleItalic">MTTS1</span>, <span class="elsevierStyleItalic">MTND1</span>, <span class="elsevierStyleItalic">MTND4</span>, <span class="elsevierStyleItalic">MTND5</span>, <span class="elsevierStyleItalic">MTND6</span>, and <span class="elsevierStyleItalic">MTND4L</span>.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Molecular Studies Available in Common Clinical Practice</span><p id="par0295" class="elsevierStylePara elsevierViewall">When a specific syndrome has been clinically identified, it is possible to direct the genetic study towards the genes responsible. If this is not feasible (family refusal, unavailability of adequate laboratory, technically complex genes, etc.) and the syndrome is clinically well defined, advice can be given assuming that the patient carries the mutation responsible for the syndrome. Conducting a karyotype may be indicated in the presence of dysmorphic features or developmental delays. It is important to remember that sometimes the signs which define the syndrome may manifest years after the onset of deafness, making it then necessary to reassess the initial diagnosis of non-syndromic hearing loss.</p><p id="par0300" class="elsevierStylePara elsevierViewall">In case of non-syndromic sensorineural hearing loss, genetic tests are the diagnostic test of choice.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,14,16,26,27</span></a> In order for genetic studies to become part of routine clinical practice it is important that their results can be obtained within a reasonable time. Faster results will lead to less anxiety for patients and/or their parents, and will enable physicians to adapt therapeutic and rehabilitative measures to the aetiological diagnosis. As mentioned, in some patients the presence of certain clinical or radiological signs and the inheritance pattern identified in the family may direct the molecular study towards specific genes (for example, <span class="elsevierStyleItalic">SLC26A4</span>, <span class="elsevierStyleItalic">POU3F4</span>, <span class="elsevierStyleItalic">OTOF</span>, or <span class="elsevierStyleItalic">MTRNR1</span>). In other cases it may be possible to select the genes to be studied through the audiometric profile (for example, mutations in the <span class="elsevierStyleItalic">WFS1</span> gene are detected in 75% of families with AD hearing loss, initially affecting only deep tones<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a>). However, in most cases it is not feasible to establish a good genotype–phenotype correlation, thus making it necessary to approach the study in an empirical manner. In addition, we must bear in mind that, depending on the particular mutation, the existence of genetic modifiers and environmental variables, it may possible for mutations in the same gene to manifest as AD or AR. It is also necessary to consider the possibility of the existence of a homozygous mutation in families with an apparently AD inheritance pattern (two or more generations affected). This may occur due to the high prevalence in our environment of carriers of mutations in the <span class="elsevierStyleItalic">GJB2</span> gene. The possibility of hearing loss appearing in double heterozygotes (carriers of mutations in <span class="elsevierStyleItalic">GJB2</span> and <span class="elsevierStyleItalic">GJB6</span> or <span class="elsevierStyleItalic">GJB2</span> and <span class="elsevierStyleItalic">GJB3</span><a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51,57</span></a>) also contributes to this pseudodominant inheritance pattern.</p><p id="par0305" class="elsevierStylePara elsevierViewall">Given the great heterogeneity of hereditary hearing loss and the prohibitive cost of studying all the genes identified so far (over 50), any molecular approach employing conventional sequencing techniques must be limited to the study of those genes most frequently mutated in the population and ethnic group to which the family belongs.<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">81,82</span></a> Therefore, the effectiveness of any genetic testing protocol will be conditioned by the knowledge of the target population (most frequent genes and mutations).<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">83</span></a> In our environment, most cases of hereditary non-syndromic hearing loss are caused by mutations in a few genes (for example, <span class="elsevierStyleItalic">GJB2</span>, <span class="elsevierStyleItalic">GJB6</span>, <span class="elsevierStyleItalic">OTOF</span>, <span class="elsevierStyleItalic">MTRNR1</span>).<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17,50</span></a> A basic study must necessarily include the <span class="elsevierStyleItalic">GJB2</span> and <span class="elsevierStyleItalic">GJB6</span> genes.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Some laboratories offer the possibility of analysing other genes among their routine tests, either sequentially or in a single experiment, employing different techniques.<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">84–86</span></a> The extreme genetic heterogeneity of hereditary hearing loss and variability in the aetiological distribution among different populations make sequential approaches inadequate in terms of efficiency and cost.<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">81,87,88</span></a> By contrast, simultaneous studies are faster and are usually easier to interpret (variants of uncertain significance, modulation of the effect of mitochondrial mutations by somatic mutations, double heterozygotes, etc.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51,87,89</span></a>). One way to solve the problem of genetic heterogeneity is through the use of gene chips. These platforms can detect predetermined point mutations within a large number of genes in a single experiment.<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">84</span></a> Since they only detect those mutations included in the chip, their efficacy is influenced by the genetic knowledge of the population in which they are employed. On the other hand, sequencing techniques do not require knowing the mutation being sought a priori.When interpreting the results of a genetic study we must bear in mind that conventional sequencing techniques are unable to identify the presence of large deletions or duplications. This requires the use of complementary techniques such as MLPA (multiplex ligation-dependent probe amplification). Both deletions and duplications of previously mentioned genes may cause hereditary hearing loss.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">51,90–92</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">When faced with a negative result we must remember that this only indicates an inability to detect a mutation in those genes analysed, but does not exclude the possibility that the cause of deafness is genetic. It is essential for this information to be correctly transmitted to patients and/or their families (for example, this would not eliminate the risk of bearing deaf children in the future).</p><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Future Perspective</span><p id="par0315" class="elsevierStylePara elsevierViewall">Currently, second-generation sequencing technologies enable the human genome to be sequenced in a single experiment within a few weeks. Their potential has been demonstrated through their application in the discovery of the genetic cause of several hereditary diseases.<a class="elsevierStyleCrossRefs" href="#bib0465"><span class="elsevierStyleSup">93–95</span></a> Recently, this technology has been used to simultaneously sequence 54 genes associated with non-syndromic hearing loss in eight deaf individuals, and succeeded in identifying the gene responsible in seven patients.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">87</span></a> At present, methodological limitations make the analysis of the sequences obtained even more complex, while the need to validate the results obtained increases the costs of the process.<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">96</span></a> However, in the future, it will be feasible to analyse the complete genome of an individual at a cost similar to that of currently sequencing a single gene with several coding exons (for example, <span class="elsevierStyleItalic">MYO7A</span> or <span class="elsevierStyleItalic">CDH23</span>) through first-generation technology (Sanger sequencing<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">97</span></a>). The future use in everyday clinical practice of second- and third-generation sequencing is expected to revolutionise clinical practice and, of course, will radically influence the management of hereditary diseases.</p></span></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of Interests</span><p id="par0320" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:2 [ "identificador" => "xres94981" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec82133" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres94980" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec82132" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Genetic Characteristics of Hereditary Hypoacusis" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Genetic Counselling" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Aetiological Diagnosis of Sensorineural Hearing Loss" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Family History" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Personal History" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Physical Examination" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Complementary Studies" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Genetic Studies" ] ] ] 8 => array:2 [ "identificador" => "sec0050" "titulo" => "Usefulness of Genetic Diagnosis" ] 9 => array:3 [ "identificador" => "sec0055" "titulo" => "Non-syndromic Genetic Hearing Loss: Genes Most Frequently Involved" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0060" "titulo" => "Connexins" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "GJB2" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "GJB6" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "GJB3" ] 3 => array:2 [ "identificador" => "sec0080" "titulo" => "OTOF" ] 4 => array:2 [ "identificador" => "sec0085" "titulo" => "COCH" ] 5 => array:2 [ "identificador" => "sec0090" "titulo" => "WFS1" ] 6 => array:2 [ "identificador" => "sec0095" "titulo" => "MIRN96" ] 7 => array:2 [ "identificador" => "sec0100" "titulo" => "POU3F4" ] ] ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Mitochondrial Genes" ] ] ] 10 => array:3 [ "identificador" => "sec0110" "titulo" => "Syndromic Genetic Hearing Loss: Most Common Syndromes" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0115" "titulo" => "Autosomal Recessive Inheritance" ] 1 => array:2 [ "identificador" => "sec0120" "titulo" => "Autosomal Dominant Inheritance" ] 2 => array:2 [ "identificador" => "sec0125" "titulo" => "X-linked Inheritance" ] 3 => array:2 [ "identificador" => "sec0130" "titulo" => "Mitochondrial Inheritance" ] ] ] 11 => array:3 [ "identificador" => "sec0135" "titulo" => "Molecular Studies Available in Common Clinical Practice" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0140" "titulo" => "Future Perspective" ] ] ] 12 => array:2 [ "identificador" => "sec0145" "titulo" => "Conflict of Interests" ] 13 => array:2 [ "identificador" => "xack35149" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2011-02-16" "fechaAceptado" => "2011-02-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec82133" "palabras" => array:7 [ 0 => "Genetic counselling" 1 => "Hereditary hearing loss" 2 => "Deafness" 3 => "Sensorineural hearing loss" 4 => "Syndromic hearing loss" 5 => "Nonsyndromic hearing loss" 6 => "<span class="elsevierStyleItalic">GJB2</span>" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec82132" "palabras" => array:7 [ 0 => "Consejo genético" 1 => "Hipoacusia hereditaria" 2 => "Sordera" 3 => "Hipoacusia neurosensorial" 4 => "Hipoacusia sindrómica" 5 => "Hipoacusia no sindrómica" 6 => "<span class="elsevierStyleItalic">GJB2</span>" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this review is to provide an updated overview of hereditary hearing loss, with special attention to the etiological diagnosis of sensorineural hearing loss, the genes most frequently mutated in our environment, the techniques available for their analysis and the clinical implications of genetic diagnosis.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">More than 60% of childhood sensorineural hearing loss is genetic. In adults, the percentage of hereditary hearing loss is unknown. Genetic testing is the highest yielding test for evaluating patients with sensorineural hearing loss. The process of genetic counselling is intended to inform patients and their families of the medical, psychological, and familial implications of genetic diseases, as well as the risks, benefits and limitations of genetic testing. The implementation of any genetic analysis must be always preceded by an appropriate genetic counselling process.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El objetivo de esta revisión es proporcionar una visión actualizada de las hipoacusias hereditarias, prestando especial atención al diagnóstico etiológico de las hipoacusias neurosensoriales, a los genes más frecuentemente mutados en nuestro medio, a las técnicas disponibles para su estudio y a las implicaciones clínicas del diagnóstico genético.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Al menos el 60% de las hipoacusias neurosensoriales infantiles tienen una causa genética. En los adultos desconocemos el porcentaje de hipoacusias hereditarias. Ante una hipoacusia neurosensorial, la prueba con un mayor rendimiento diagnóstico son los análisis genéticos. El proceso de consejo o asesoramiento genético tiene como fin informar al paciente y sus familiares de la probabilidad de presentar una enfermedad condicionada genéticamente, del riesgo de transmitirla, de las medidas de prevención y diagnóstico precoz disponibles, y de la posibilidad de llevar a cabo un estudio genético. La realización de cualquier análisis genético, siempre ha de venir precedida por el adecuado proceso de asesoramiento genético.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Cabanillas Farpón R, Cadiñanos Bañales J. Hipoacusias hereditarias: asesoramiento genético. Acta Otorrinolaringol Esp. 2012;63:218–29.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Autosomal Recessive Inheritance</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Locus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Locus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB1A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GJB2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connexin 26<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">CLDN14</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Claudin 14 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB1B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GJB6</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connexin 30<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO3A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin IIIA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO7A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin VIIA<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">WHRN</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Whirlin <a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO15A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin XVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">ESRRB</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESRRB \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">SLC26A4</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pendrin<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">ESPN</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ESPN \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TMIE</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TMIE \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO6</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin VI<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB7/DFNB11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TMC1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TMC1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">HGF</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hepatocyte growth factor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB8/DFNB10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TMPRSS3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TMPRSS3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MARVELD2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MARVELD2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">OTOF</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Otoferlin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">COL11A2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Collagen XI, α2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">CDH23</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cadherin23<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">PJVK</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Pejvakin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">STRC</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Stereocilin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">SLC26A5</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prestina \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">USH1C</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Harmonin<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">LRTOMT</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LRTOMT \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TECTA</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tectorin-α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB66/67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">LHFPL5</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LHFPL5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">OTOA</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Otoancorin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DNFB77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">LOXHD1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LOXHD1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">PCDH15</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Protocadherin 15<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TPRN</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Taperin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">RDX</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Radixin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GPSM2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GPSM2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GRXCR1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GRXCR1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">PTPRQ</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PTPRQ \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNB28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TRIOBP</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TRIOBP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GJB3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connexin 31<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179754.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">These genes can also cause syndromic hearing loss.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Genes Involved in Non-syndromic Genetic Hearing Loss With Autosomal Recessive Inheritance.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="6" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Autosomal Dominant Inheritance</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Locus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Locus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">DIAPH1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DIAPH1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">COL11A2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Collagen XI, α2<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA2A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">KCNQ4</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KCNQ4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">POU4F3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">POU4F3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA2B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GJB3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connexin 31<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYH9</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MYH9<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA3A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GJB2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connexin 26<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA20/26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">ACTG1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">γ1-Actin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA3B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GJB6</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Connexin 30<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO6</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin VI<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYH14</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">MYH14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">GRHL2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">GRHL2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">DFNA5</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TMC1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TMC1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA6/DFNA14/DFNA38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">WFS1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Wolframin<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">CCDC50</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CCDC50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA8/DFNA12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TECTA</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tectorin α \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO1A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin IA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">COCH</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cochlin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MIRN96</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Micro-RNA 96 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">EYA4</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EYA4<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TJP2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Tight junction protein 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNA11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MYO7A</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Myosin VIIA<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">CRYM</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">μ-crystallin \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179755.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">These genes may also cause syndromic hearing loss.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Genes Involved in Non-syndromic Genetic Hearing Loss With Autosomal Dominant Inheritance.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">X-linked Inheritance</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Locus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNX1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">PRPS1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Phosphoribosylpyrophosphate synthetase 1<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DFNX2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">POU3F4</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">POU3F4 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179757.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Mitochondrial Inheritance</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Gene \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Protein \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MTRNR1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ribosomal mitochondrial 12S RNA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">MTTS1</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mitochondrial serine transfer 1 RNA<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab179756.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara">These genes may also cause syndromic hearing loss.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Genes Involved in Non-syndromic Genetic Hearing Loss With X-linked or Mitochondrial Inheritance.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:97 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical aspects of hereditary hearing loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097GIM.0b013e3180980bd0" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2007" "volumen" => "9" "paginaInicial" => "393" "paginaFinal" => "408" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exploring the clinical and epidemiological complexity of GJB2-linked deafness" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.10621" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2002" "volumen" => "112" "paginaInicial" => "38" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1203/pdr.0b013e3180536609" "Revista" => array:6 [ "tituloSerie" => "Pediatr Res" "fecha" => "2007" "volumen" => "61" "paginaInicial" => "687" "paginaFinal" => "691" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2008" "volumen" => "83" "paginaInicial" => "401" "paginaFinal" => "407" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Variations in HSP70 genes associated with noise-induced hearing loss in two independent populations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ejhg.2008.172" "Revista" => array:6 [ "tituloSerie" => "Eur J Hum Genet" "fecha" => "2009" "volumen" => "17" "paginaInicial" => "329" "paginaFinal" => "335" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mitochondrial deafness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-0004.2007.00800.x" "Revista" => array:6 [ "tituloSerie" => "Clin Genet" "fecha" => "2007" "volumen" => "71" "paginaInicial" => "379" "paginaFinal" => "391" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:1 [ "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:2 [ "titulo" => "Hereditary hearing loss and its syndromes" "serieFecha" => "2004" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Van Camp G, Smith RJH. The hereditary hearing loss homepage [accessed 18/01/11]. Available at: <a class="elsevierStyleInterRef" href="http://hereditaryhearingloss.org/">http://hereditaryhearingloss.org/</a>" ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etiologic diagnosis of sensorineural hearing loss in adults" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.otohns.2005.03.001" "Revista" => array:6 [ "tituloSerie" => "Otolaryngol Head Neck Surg" "fecha" => "2005" "volumen" => "132" "paginaInicial" => "890" "paginaFinal" => "895" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Waardenburg syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "1997" "volumen" => "34" "paginaInicial" => "656" "paginaFinal" => "665" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the Wolfram syndrome type 1 gene (WFS1) define a clinical entity of dominant low-frequency sensorineural hearing loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archotol.129.4.411" "Revista" => array:7 [ "tituloSerie" => "Arch Otolaryngol Head Neck Surg" "fecha" => "2003" "volumen" => "129" "paginaInicial" => "411" "paginaFinal" => "420" "link" => array:1 [ 0 => array:2 [ …2] ] "itemHostRev" => array:3 [ "pii" => "S0140673610608355" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Diab Med" "fecha" => "2008" "volumen" => "25" "paginaInicial" => "657" "paginaFinal" => "661" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The implications of genetic testing for deafness" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ …1] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.AUD.0000079800.64741.CF" "Revista" => array:6 [ "tituloSerie" => "Ear Hear" "fecha" => "2003" "volumen" => "24" "paginaInicial" => "324" "paginaFinal" => "331" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early hearing detection and intervention: 2010 CODEPEH recommendation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ …5] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0001-6519(10)71249-8" "Revista" => array:7 [ "tituloSerie" => "Acta Otorrinolaringol Esp" "fecha" => "2010" "volumen" => "61" "paginaInicial" => "69" "paginaFinal" => "77" "link" => array:1 [ 0 => array:2 [ …2] ] "itemHostRev" => array:3 [ "pii" => "S0959289X10001962" "estado" => "S300" "issn" => "0959289X" ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Otol Neurotol" "fecha" => "2005" "volumen" => "26" "paginaInicial" => "610" "paginaFinal" => "615" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comprehensive diagnostic battery for evaluating sensorineural hearing loss in children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MAO.0b013e31820160fa" "Revista" => array:6 [ "tituloSerie" => "Otol Neurotol" "fecha" => "2011" "volumen" => "32" "paginaInicial" => "259" "paginaFinal" => "264" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Q829X, a novel mutation in the gene encoding otoferlin (OTOF), is frequently found in Spanish patients with prelingual non-syndromic hearing loss" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2002" "volumen" => "39" "paginaInicial" => "502" "paginaFinal" => "506" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "De novo mutation in the gene encoding connexin-26 (GJB2) in a sporadic case of keratitis-ichthyosisdeafness (KID) syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.a.10851" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet A" "fecha" => "2003" "volumen" => "117A" "paginaInicial" => "89" "paginaFinal" => "91" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical evaluation of the hearingimpaired infant" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ …2] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Otolaryngol Clin North Am" "fecha" => "1999" "volumen" => "32" "paginaInicial" => "1019" "paginaFinal" => "1035" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of laboratory evaluation and radiologic imaging in the diagnostic evaluation of children with sensorineural hearing loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.mlg.0000200750.74249.79" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2002" "volumen" => "112" "paginaInicial" => "1" "paginaFinal" => "7" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Establishing the etiology of childhood hearing loss" "autores" => array:1 [ 0 => array:2 [ "etal" => false …1 ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Otolaryngol Head Neck Surg" "fecha" => "1999" "volumen" => "120" "paginaInicial" => "159" "paginaFinal" => "163" "link" => array:1 [ …1] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ejhg.5201611" "Revista" => array:6 [ "tituloSerie" => "Eur J Hum Genet" "fecha" => "2006" "volumen" => "14" "paginaInicial" => "773" "paginaFinal" => "779" "link" => array:1 [ …1] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Genet" "fecha" => "1999" "volumen" => "104" "paginaInicial" => "188" "paginaFinal" => "192" "link" => array:1 [ …1] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Audiologic and temporal bone imaging findings in patients with sensorineural hearing loss and GJB2 mutations" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/lary.20162" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2009" "volumen" => "119" "paginaInicial" => "554" "paginaFinal" => "558" "link" => array:1 [ …1] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Temporal bone computed tomography findings in bilateral sensorineural hearing loss" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Dis Child" "fecha" => "2000" "volumen" => "82" "paginaInicial" => "257" "paginaFinal" => "260" "link" => array:1 [ …1] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of clinical examination and genetic testing of 500 individuals with hearing loss evaluated through a genetics of hearing loss clinic" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.a.31179" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2006" "volumen" => "140" "paginaInicial" => "827" "paginaFinal" => "836" "link" => array:1 [ …1] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hereditary deafness" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Med Genet" "fecha" => "1999" "volumen" => "89" "paginaInicial" => "121" "paginaFinal" => "122" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment of aminoglycosides" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "1998" "volumen" => "62" "paginaInicial" => "27" "paginaFinal" => "35" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.478" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "1345" "paginaFinal" => "1349" "link" => array:1 [ …1] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical features of patients with GJB2 (connexin 26) mutations: severity of hearing loss is correlated with genotypes and protein expression patterns" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10038-004-0223-7" "Revista" => array:6 [ "tituloSerie" => "J Hum Genet" "fecha" => "2005" "volumen" => "50" "paginaInicial" => "76" "paginaFinal" => "83" "link" => array:1 [ …1] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GJB2 mutations and degree of hearing loss: a multicenter study" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/497996" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2005" "volumen" => "77" "paginaInicial" => "945" "paginaFinal" => "957" "link" => array:1 [ …1] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Performance of cochlear implant recipients with GJB2-related deafness" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.10330" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2002" "volumen" => "109" "paginaInicial" => "167" "paginaFinal" => "170" "link" => array:1 [ …1] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of GJB2 allele variants on performance after cochlear implantation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00005537-200312000-00015" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2003" "volumen" => "113" "paginaInicial" => "2135" "paginaFinal" => "2140" "link" => array:1 [ …1] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Preservation of hearing in cochlear implant surgery: advantages of combined electrical and acoustical speech processing" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.MLG.0000157695.07536.D2" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2005" "volumen" => "115" "paginaInicial" => "796" "paginaFinal" => "802" "link" => array:1 [ …1] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutation in the COCH gene is associated with superior semicircular canal dehiscence" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.a.32618" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet A" "fecha" => "2009" "volumen" => "149A" "paginaInicial" => "280" "paginaFinal" => "285" "link" => array:1 [ …1] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correction of progressive hearing loss in superior canal dehiscence syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MLG.0b013e31814b8d67" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2008" "volumen" => "118" "paginaInicial" => "10" "paginaFinal" => "13" "link" => array:1 [ …1] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Results of cochlear implantation in two children with mutations in the OTOF gene" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ijporl.2005.09.006" "Revista" => array:6 [ "tituloSerie" => "Int J Pediatr Otorhinolaryngol" "fecha" => "2006" "volumen" => "70" "paginaInicial" => "689" "paginaFinal" => "696" "link" => array:1 [ …1] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1829" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2006" "volumen" => "38" "paginaInicial" => "770" "paginaFinal" => "778" "link" => array:1 [ …1] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cochlear implantation in children with auditory neuropathy spectrum disorder" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/AUD.0b013e3181ce693b" "Revista" => array:6 [ "tituloSerie" => "Ear Hear" "fecha" => "2010" "volumen" => "31" "paginaInicial" => "325" "paginaFinal" => "335" "link" => array:1 [ …1] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Am Med Assoc" "fecha" => "1999" "volumen" => "281" "paginaInicial" => "2211" "paginaFinal" => "2216" ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advances in molecular and cellular therapies for hearing loss" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.mt.6300351" "Revista" => array:6 [ "tituloSerie" => "Mol Ther" "fecha" => "2008" "volumen" => "16" "paginaInicial" => "224" "paginaFinal" => "236" "link" => array:1 [ …1] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2010.02.003" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2010" "volumen" => "86" "paginaInicial" => "479" "paginaFinal" => "484" "link" => array:1 [ …1] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in LOXHD1, an evolutionarily conserved stereociliary protein, disrupt hair cell function in mice and cause progressive hearing loss in humans" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2009.07.017" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2009" "volumen" => "85" "paginaInicial" => "328" "paginaFinal" => "337" "link" => array:1 [ …1] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gap junctions and connexins in the inner ear: their roles in homeostasis and deafness" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MOO.0b013e32830e20b0" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Otolaryngol Head Neck Surg" "fecha" => "2008" "volumen" => "16" "paginaInicial" => "452" "paginaFinal" => "457" "link" => array:1 [ …1] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/humu.20958" "Revista" => array:6 [ "tituloSerie" => "Hum Mutat" "fecha" => "2009" "volumen" => "30" "paginaInicial" => "724" "paginaFinal" => "733" "link" => array:1 [ …1] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: a HuGE review" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/00125817-200207000-00004" "Revista" => array:6 [ "tituloSerie" => "Genet Med" "fecha" => "2002" "volumen" => "4" "paginaInicial" => "258" "paginaFinal" => "274" "link" => array:1 [ …1] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High carrier frequency of the 35delG deafness mutation in European populations. Genetic Analysis Consortium of GJB2 35delG" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.ejhg.5200406" "Revista" => array:7 [ "tituloSerie" => "Eur J Hum Genet" "fecha" => "2000" "volumen" => "8" "paginaInicial" => "19" "paginaFinal" => "23" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GJB2 mutations in hearing impairment: identification of a broad clinical spectrum for improved genetic counseling" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.mlg.0000157855.47143.71" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2005" "volumen" => "115" "paginaInicial" => "461" "paginaFinal" => "465" "link" => array:1 [ …1] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0245" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A missense mutation in connexin26, D66H, causes mutilating keratoderma with sensorineural deafness (Vohwinkel's syndrome) in three unrelated families" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "1999" "volumen" => "8" "paginaInicial" => "1237" "paginaFinal" => "1243" "link" => array:1 [ …1] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0250" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of the 35delG mutation in the GJB2 gene, del (GJB6-D13S1830) in the GJB6 gene, Q829X in the OTOF gene and A1555G in the mitochondrial 12S rRNA gene in subjects with non-syndromic sensorineural hearing impairment of congenital/childhood onset" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Acta Otorrinolaringol Esp" "fecha" => "2005" "volumen" => "56" "paginaInicial" => "463" "paginaFinal" => "468" "link" => array:1 [ …1] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0255" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmg.2004.028324" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2005" "volumen" => "42" "paginaInicial" => "588" "paginaFinal" => "594" "link" => array:1 [ …1] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0260" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in GJB6 cause nonsyndromic autosomal dominant deafness at DFNA3 locus" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/12612" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "1999" "volumen" => "23" "paginaInicial" => "16" "paginaFinal" => "18" "link" => array:1 [ …1] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0265" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in GJB6 cause hidrotic ectodermal dysplasia" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/79851" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2000" "volumen" => "26" "paginaInicial" => "142" "paginaFinal" => "144" "link" => array:1 [ …1] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0270" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in connexin31 underlie recessive as well as dominant non-syndromic hearing loss" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "2000" "volumen" => "9" "paginaInicial" => "63" "paginaFinal" => "67" "link" => array:1 [ …1] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0275" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Connexin 31 (GJB3) is expressed in the peripheral and auditory nerves and causes neuropathy and hearing impairment" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "2001" "volumen" => "10" "paginaInicial" => "947" "paginaFinal" => "952" "link" => array:1 [ …1] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0280" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A mutation in GJB3 is associated with recessive erythrokeratodermia variabilis (EKV) and leads to defective trafficking of the connexin 31 protein" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "2002" "volumen" => "11" "paginaInicial" => "1311" "paginaFinal" => "1316" "link" => array:1 [ …1] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0285" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26 and Cx31" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00439-008-0602-9" "Revista" => array:6 [ "tituloSerie" => "Hum Genet" "fecha" => "2009" "volumen" => "125" "paginaInicial" => "53" "paginaFinal" => "62" "link" => array:1 [ …1] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0290" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/hmg/ddp213" "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "2009" "volumen" => "18" "paginaInicial" => "2779" "paginaFinal" => "2790" "link" => array:1 [ …1] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0295" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jmg.2005.038612" "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "2006" "volumen" => "43" "paginaInicial" => "576" "paginaFinal" => "581" "link" => array:1 [ …1] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0300" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Vestibular deterioration precedes hearing deterioration in the P51S COCH mutation (DFNA9): an analysis in 74 mutation carriers" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Otol Neurotol" "fecha" => "2005" "volumen" => "26" "paginaInicial" => "918" "paginaFinal" => "925" "link" => array:1 [ …1] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0305" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wolfram (DIDMOAD) syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Med Genet" "fecha" => "1997" "volumen" => "34" "paginaInicial" => "838" "paginaFinal" => "841" "link" => array:1 [ …1] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0310" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cisd2 deficiency drives premature aging and causes mitochondriamediated defects in mice" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1101/gad.1779509" "Revista" => array:6 [ "tituloSerie" => "Genes Dev" "fecha" => "2009" "volumen" => "23" "paginaInicial" => "1183" "paginaFinal" => "1194" "link" => array:1 [ …1] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0315" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/520961" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2007" "volumen" => "81" "paginaInicial" => "673" "paginaFinal" => "683" "link" => array:1 [ …1] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0320" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phenotypegenotype correlations in a series of wolfram syndrome families" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Diab Care" "fecha" => "2004" "volumen" => "27" "paginaInicial" => "2003" "paginaFinal" => "2009" ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0325" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of novel mutations in WFS1 and genotypephenotype correlation in Wolfram syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.a.31809" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet A" "fecha" => "2007" "volumen" => "143A" "paginaInicial" => "1605" "paginaFinal" => "1612" "link" => array:1 [ …1] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0330" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Presence of a major WFS1 mutation in SpanishWolfram syndrome pedigrees" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/mgme.2000.3107" "Revista" => array:7 [ "tituloSerie" => "Mol Genet Metab" "fecha" => "2001" "volumen" => "72" "paginaInicial" => "72" "paginaFinal" => "81" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0335" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.355" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "609" "paginaFinal" => "613" "link" => array:1 [ …1] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0340" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.369" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2009" "volumen" => "41" "paginaInicial" => "614" "paginaFinal" => "618" "link" => array:1 [ …1] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0345" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Xlinked deafness, stapes gushers and a distinctive defect of the inner ear" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Neuroradiology" "fecha" => "1991" "volumen" => "33" "paginaInicial" => "326" "paginaFinal" => "330" "link" => array:1 [ …1] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0350" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Mol Genet" "fecha" => "1995" "volumen" => "4" "paginaInicial" => "1467" "paginaFinal" => "1469" "link" => array:1 [ …1] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0355" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Audiological and genetic features of the mtDNA mutations" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/00016480701719011" "Revista" => array:6 [ "tituloSerie" => "Acta Otolaryngol" "fecha" => "2008" "volumen" => "128" "paginaInicial" => "732" "paginaFinal" => "738" "link" => array:1 [ …1] ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0360" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An update on the genetics of usher syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2011/417217" "Revista" => array:5 [ "tituloSerie" => "J Ophthalmol" "fecha" => "2011" "volumen" => "2011" "paginaInicial" => "417217" "link" => array:1 [ …1] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0365" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differential diagnosis between Pendred and pseudo-Pendred syndromes: clinical, radiologic, and molecular studies" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1203/00006450-200204000-00013" "Revista" => array:6 [ "tituloSerie" => "Pediatr Res" "fecha" => "2002" "volumen" => "51" "paginaInicial" => "479" "paginaFinal" => "484" "link" => array:1 [ …1] ] ] ] ] ] ] 73 => array:3 [ "identificador" => "bib0370" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4)" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/518314" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2007" "volumen" => "80" "paginaInicial" => "1055" "paginaFinal" => "1063" "link" => array:1 [ …1] ] ] ] ] ] ] 74 => array:3 [ "identificador" => "bib0375" "etiqueta" => "75" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The genetic basis of long QT and short QT syndromes: a mutation update" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/humu.21106" "Revista" => array:6 [ "tituloSerie" => "Hum Mutat" "fecha" => "2009" "volumen" => "30" "paginaInicial" => "1486" "paginaFinal" => "1511" "link" => array:1 [ …1] ] ] ] ] ] ] 75 => array:3 [ "identificador" => "bib0380" "etiqueta" => "76" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Review and update of mutations causing Waardenburg syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/humu.21211" "Revista" => array:6 [ "tituloSerie" => "Hum Mutat" "fecha" => "2010" "volumen" => "31" "paginaInicial" => "391" "paginaFinal" => "406" "link" => array:1 [ …1] ] ] ] ] ] ] 76 => array:3 [ "identificador" => "bib0385" "etiqueta" => "77" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/513322" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2007" "volumen" => "80" "paginaInicial" => "800" "paginaFinal" => "804" "link" => array:1 [ …1] ] ] ] ] ] ] 77 => array:3 [ "identificador" => "bib0390" "etiqueta" => "78" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Branchio-otorenal syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajmg.a.31561" "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet A" "fecha" => "2007" "volumen" => "143A" "paginaInicial" => "1671" "paginaFinal" => "1678" "link" => array:1 [ …1] ] ] ] ] ] ] 78 => array:3 [ "identificador" => "bib0395" "etiqueta" => "79" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1523-1755.2002.00379.x" "Revista" => array:6 [ "tituloSerie" => "Kidney Int" "fecha" => "2002" "volumen" => "61" "paginaInicial" => "1947" "paginaFinal" => "1956" "link" => array:1 [ …1] ] ] ] ] ] ] 79 => array:3 [ "identificador" => "bib0400" "etiqueta" => "80" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mutational spectrum of the WFS1 gene inWolfram syndrome, nonsyndromic hearing impairment, diabetes mellitus, and psychiatric disease" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/humu.10258" "Revista" => array:6 [ "tituloSerie" => "Hum Mutat" "fecha" => "2003" "volumen" => "22" "paginaInicial" => "275" "paginaFinal" => "287" "link" => array:1 [ …1] ] ] ] ] ] ] 80 => array:3 [ "identificador" => "bib0405" "etiqueta" => "81" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Forty-six genes causing nonsyndromic hearing impairment: which ones should be analyzed in DNA diagnostics?" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.mrrev.2008.08.002" "Revista" => array:7 [ "tituloSerie" => "Mutat Res" "fecha" => "2009" "volumen" => "681" "paginaInicial" => "189" "paginaFinal" => "196" "link" => array:1 [ …1] "itemHostRev" => array:3 [ …3] ] ] ] ] ] ] 81 => array:3 [ "identificador" => "bib0410" "etiqueta" => "82" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Molecular basis of childhood deafness resulting from mutations in the GJB2 (connexin 26) gene" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Genet" "fecha" => "2000" "volumen" => "106" "paginaInicial" => "40" "paginaFinal" => "44" "link" => array:1 [ …1] ] ] ] ] ] ] 82 => array:3 [ "identificador" => "bib0415" "etiqueta" => "83" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic yield in the workup of congenital sensorineural hearing loss is dependent on patient ethnicity" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MAO.0b013e3181fc786f" "Revista" => array:6 [ "tituloSerie" => "Otol Neurotol" "fecha" => "2011" "volumen" => "32" "paginaInicial" => "81" "paginaFinal" => "87" "link" => array:1 [ …1] ] ] ] ] ] ] 83 => array:3 [ "identificador" => "bib0420" "etiqueta" => "84" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: a new approach for newborn screening follow-up" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2005-2519" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2006" "volumen" => "118" "paginaInicial" => "985" "paginaFinal" => "994" "link" => array:1 [ …1] ] ] ] ] ] ] 84 => array:3 [ "identificador" => "bib0425" "etiqueta" => "85" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High-throughput detection of mutations responsible for childhood hearing loss using resequencing microarrays" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1472-6750-10-10" "Revista" => array:5 [ "tituloSerie" => "BMC Biotechnol" "fecha" => "2010" "volumen" => "10" "paginaInicial" => "10" "link" => array:1 [ …1] ] ] ] ] ] ] 85 => array:3 [ "identificador" => "bib0430" "etiqueta" => "86" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Application of SNaPshot multiplex assays for simultaneous multigene mutation screening in patients with idiopathic sensorineural hearing impairment" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/lary.20621" "Revista" => array:6 [ "tituloSerie" => "Laryngoscope" "fecha" => "2009" "volumen" => "119" "paginaInicial" => "2411" "paginaFinal" => "2416" "link" => array:1 [ …1] ] ] ] ] ] ] 86 => array:3 [ "identificador" => "bib0435" "etiqueta" => "87" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comprehensive genetic testing for hereditary hearing loss using massively parallel sequencing" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1073/pnas.1012989107" "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "2010" "volumen" => "107" "paginaInicial" => "21104" "paginaFinal" => "21109" "link" => array:1 [ …1] ] ] ] ] ] ] 87 => array:3 [ "identificador" => "bib0440" "etiqueta" => "88" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic counselling in visual and auditory disorders" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Soc Esp Oftalmol" "fecha" => "2008" "volumen" => "83" "paginaInicial" => "689" "paginaFinal" => "702" "link" => array:1 [ …1] ] ] ] ] ] ] 88 => array:3 [ "identificador" => "bib0445" "etiqueta" => "89" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Connexin 26 gene (GJB2) mutation modulates the severity of hearing loss associated with the 1555A→G mitochondrial mutation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Med Genet" "fecha" => "2001" "volumen" => "103" "paginaInicial" => "334" "paginaFinal" => "338" "link" => array:1 [ …1] ] ] ] ] ] ] 89 => array:3 [ "identificador" => "bib0450" "etiqueta" => "90" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genomic duplication and overexpression of TJP2/ZO-2 leads to altered expression of apoptosis genes in progressive nonsyndromic hearing loss DFNA51" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2010.05.011" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2010" "volumen" => "87" "paginaInicial" => "101" "paginaFinal" => "109" "link" => array:1 [ …1] ] ] ] ] ] ] 90 => array:3 [ "identificador" => "bib0455" "etiqueta" => "91" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A deletion involving the connexin 30 gene in nonsyndromic hearing impairment" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa012052" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "346" "paginaInicial" => "243" "paginaFinal" => "249" "link" => array:1 [ …1] ] ] ] ] ] ] 91 => array:3 [ "identificador" => "bib0460" "etiqueta" => "92" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical evaluation of DFN3 patients with deletions in the POU3F4 locus and detection of carrier female using MLPA" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1399-0004.2010.01426.x" "Revista" => array:6 [ "tituloSerie" => "Clin Genet" "fecha" => "2010" "volumen" => "78" "paginaInicial" => "524" "paginaFinal" => "532" "link" => array:1 [ …1] ] ] ] ] ] ] 92 => array:3 [ "identificador" => "bib0465" "etiqueta" => "93" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Analysis of genetic inheritance in a family quartet by whole-genome sequencing" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1186802" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2010" "volumen" => "328" "paginaInicial" => "636" "paginaFinal" => "639" "link" => array:1 [ …1] ] ] ] ] ] ] 93 => array:3 [ "identificador" => "bib0470" "etiqueta" => "94" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa0908094" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2010" "volumen" => "362" "paginaInicial" => "1181" "paginaFinal" => "1191" "link" => array:1 [ …1] ] ] ] ] ] ] 94 => array:3 [ "identificador" => "bib0475" "etiqueta" => "95" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng.653" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2010" "volumen" => "42" "paginaInicial" => "827" "paginaFinal" => "829" "link" => array:1 [ …1] ] ] ] ] ] ] 95 => array:3 [ "identificador" => "bib0480" "etiqueta" => "96" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sequencing technologies – the next generation" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nrg2626" "Revista" => array:6 [ "tituloSerie" => "Nat Rev Genet" "fecha" => "2010" "volumen" => "11" "paginaInicial" => "31" "paginaFinal" => "46" "link" => array:1 [ …1] ] ] ] ] ] ] 96 => array:3 [ "identificador" => "bib0485" "etiqueta" => "97" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "DNA sequencing with chain-terminating inhibitors" "autores" => array:1 [ 0 => array:2 [ …2] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Proc Natl Acad Sci USA" "fecha" => "1977" "volumen" => "74" "paginaInicial" => "5463" "paginaFinal" => "5467" "link" => array:1 [ …1] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "identificador" => "xack35149" "titulo" => "Acknowledgements" "texto" => "<p id="par0325" class="elsevierStylePara elsevierViewall">Research projects at the Oncology and Molecular Medicine Institute of Asturias are funded by the <span class="elsevierStyleGrantSponsor">Maria Cristina Masaveu-Peterson Foundation</span>, the <span class="elsevierStyleGrantSponsor">Medical Centre of Asturias Foundation</span> and the <span class="elsevierStyleGrantSponsor">Cajastur social work project</span>.</p>" ] ] ] "idiomaDefecto" => "en" "url" => "/21735735/0000006300000003/v1_201304231514/S2173573512000476/v1_201304231514/en/main.assets" "Apartado" => array:4 [ "identificador" => "5885" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review Article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735735/0000006300000003/v1_201304231514/S2173573512000476/v1_201304231514/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173573512000476?idApp=UINPBA00004N" ]
Información de la revista
Compartir
Descargar PDF
Más opciones de artículo
Review article
Hereditary Hearing Loss: Genetic Counselling
Hipoacusias hereditarias: asesoramiento genético