Letter to the Editor
A novel TTN variant in a patient with distal myopathy of lower limbs and dilated cardiomyopathy
Una nueva variante en el gen de la titina en un paciente con miopatía distal de miembros inferiores y miocardiopatía dilatada
Read
1572
Timeswas read the article
272
Total PDF
1300
Total HTML
Share statistics
array:24 [ "pii" => "S2173580821001085" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2021.01.001" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1561" "copyrightAnyo" => "2021" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:721-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0213485321000049" "issn" => "02134853" "doi" => "10.1016/j.nrl.2021.01.001" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1561" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:721-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta al Editor</span>" "titulo" => "Una nueva variante en el gen de la titina en un paciente con miopatía distal de miembros inferiores y miocardiopatía dilatada" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "721" "paginaFinal" => "723" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "A novel TTN variant in a patient with distal myopathy of lower limbs and dilated cardiomyopathy" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1612 "Ancho" => 1007 "Tamanyo" => 65046 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">RM muscular, corte axial, secuencia T2: atrofia con reemplazo graso de la musculatura extensora de MMII.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Lopez-Bravo, J.C. Roche-Bueno, A. Romera-López, P. Larrode-Pellicer" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Lopez-Bravo" ] 1 => array:2 [ "nombre" => "J.C." "apellidos" => "Roche-Bueno" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Romera-López" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Larrode-Pellicer" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173580821001085" "doi" => "10.1016/j.nrleng.2021.01.001" "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/S2173580821001085?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485321000049?idApp=UINPBA00004N" "url" => "/02134853/0000003600000009/v1_202110170532/S0213485321000049/v1_202110170532/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2173580821001097" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.12.002" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1560" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:723-5" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Spontaneous spinal epidural haematoma and nonaneurysmal subarachnoid haemorrhage in a patient with eosinophilic granulomatosis with polyangiitis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "723" "paginaFinal" => "725" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hematoma epidural espinal espontáneo y hemorragia subaracnoidea no aneurismática en paciente con granulomatosis eosinofílica con poliangitis" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2461 "Ancho" => 1008 "Tamanyo" => 267162 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A) T1-weighted MRI study of the spine (sagittal plane), showing epidural haemorrhage of the thoracolumbar spine. Loculi with greater posterior blood pooling are observed at the T12-L1 and S1-S2 levels. The morphology of the spinal cord is normal. B) Non-contrast head CT scan showing perimesencephalic, intraventricular, and cerebellar subarachnoid haemorrhage (Fisher grade IV).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Lázaro Romero, A. Carilla Sanromán, L. Horna Cañete, M. Serrano Ponz" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Lázaro Romero" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Carilla Sanromán" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Horna Cañete" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Serrano Ponz" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485321000037" "doi" => "10.1016/j.nrl.2020.12.003" "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/S0213485321000037?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821001097?idApp=UINPBA00004N" "url" => "/21735808/0000003600000009/v1_202110290547/S2173580821001097/v1_202110290547/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2173580821001061" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2020.11.012" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1554" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2021;36:719-21" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Meningoencephalitis caused by <span class="elsevierStyleItalic">Cryptococcus neoformans</span> and varicella-zoster virus in a patient with systemic lupus erythematosus" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "719" "paginaFinal" => "721" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Meningoencefalitis por <span class="elsevierStyleItalic">Cryptococcus neoformans</span> y virus varicela-zoster en paciente con lupus eritematoso sistémico" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1004 "Ancho" => 1674 "Tamanyo" => 140746 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Axial T1-weighted sequence with contrast administration showing leptomeningeal enhancement. (B) Axial T2-weighted sequence showing dilated Virchow-Robin spaces (arrows).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. Cabezudo-García, M.V. Castro-Sánchez, N. Mena-Vázquez, A. Fernández-Nebro" "autores" => array:4 [ 0 => array:2 [ "nombre" => "P." "apellidos" => "Cabezudo-García" ] 1 => array:2 [ "nombre" => "M.V." "apellidos" => "Castro-Sánchez" ] 2 => array:2 [ "nombre" => "N." "apellidos" => "Mena-Vázquez" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Fernández-Nebro" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485320304382" "doi" => "10.1016/j.nrl.2020.11.010" "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/S0213485320304382?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821001061?idApp=UINPBA00004N" "url" => "/21735808/0000003600000009/v1_202110290547/S2173580821001061/v1_202110290547/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "A novel <span class="elsevierStyleItalic">TTN</span> variant in a patient with distal myopathy of lower limbs and dilated cardiomyopathy" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "721" "paginaFinal" => "723" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Lopez-Bravo, J.C. Roche-Bueno, A. Romera-López, P. Larrode-Pellicer" "autores" => array:4 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Lopez-Bravo" "email" => array:1 [ 0 => "alba.lopez.bravo@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.C." "apellidos" => "Roche-Bueno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Romera-López" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "P." "apellidos" => "Larrode-Pellicer" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Sección de Neurología, Hospital Reina Sofía, Tudela, Navarra, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación Sanitaria Aragón (IIS-A), Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Genética Médica, Sistemas Genómicos, Valencia, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Una nueva variante en el gen de la titina en un paciente con miopatía distal de miembros inferiores y miocardiopatía dilatada" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1612 "Ancho" => 1007 "Tamanyo" => 65046 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Muscle MRI (axial plane, T2-weighted sequence): atrophy with fat replacement in the extensor muscles of the lower limbs.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Titin is a sarcomeric protein expressed in the cardiac and skeletal muscles. It is encoded by a single gene, <span class="elsevierStyleItalic">TTN</span>, located on the long arm of chromosome 2.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a><span class="elsevierStyleItalic">TTN</span> gene mutations have been associated with a wide range of cardiomyopathies and skeletal muscle disorders (late-onset tibial muscular dystrophy, early-onset recessive distal titinopathy, autosomal recessive limb-girdle muscular dystrophy-10, etc).<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Tibial muscular dystrophy (TMD), also known as Udd distal myopathy (late-onset, type 2a), is characterised by late onset (between the ages of 35 and 55 years) and slow progression, and usually only affects the muscles of the anterior compartment of the lower limbs.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> These patients present normal or slightly elevated serum creatine kinase levels, with EMG results suggestive of myopathy.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,4</span></a> Muscle biopsy results reveal variability in fibre size, central nuclei, necrosis, fibroadipose tissue, and rimmed vacuoles.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Muscle MRI reveals selective fat replacement in the muscles of the anterior compartments of the lower limbs.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of a 37-year-old man with lower limb weakness and muscle atrophy affecting the peroneal and tibialis anterior muscles and the extensor muscles of the toes. He had no history of diabetes mellitus, cancer, or connective tissue disorders. A cardiac comorbidity was also detected, and the patient was diagnosed with dilated non-ischaemic cardiomyopathy. His parents were non-consanguineous, and he had family history of muscle disease of unknown origin in a maternal uncle, who presented weakness and muscle atrophy in the lower limbs. To date, his parents have not consulted due to neurological or cardiac symptoms.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The neurological examination revealed atrophy and weakness in the muscles of the anterior compartment of the lower limbs, with asymmetric weakness of ankle dorsiflexion (right, 1/5; left, 3/5). He was unable to toe walk as a result of the poor dorsiflexion.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A blood analysis including muscle enzymes and a mitochondrial respiratory chain enzyme assay yielded normal results. Electroneurography showed no alterations, and the EMG study revealed low-amplitude polyphasic motor unit potentials with early recruitment of the tibialis anterior muscles; these findings are compatible with a chronic myopathic process. A biopsy study of the quadriceps revealed myopathic alterations with nuclear centralisation and vacuolar degeneration, with no ragged red fibres and normal COX staining.</p><p id="par0025" class="elsevierStylePara elsevierViewall">An MRI scan of the muscles of the lower limbs (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) revealed atrophy with fat replacement in the extensor muscles (tibialis anterior, extensor digitorum longus, and extensor hallucis longus, predominantly on the right side). A cardiac MRI scan revealed biventricular dilatation with moderate systolic dysfunction affecting both ventricles, and dilatation of both atria; these findings are compatible with non-ischaemic cardiomyopathy.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Massive sequencing of 8 genes associated with muscular dystrophies (<span class="elsevierStyleItalic">ANO5</span>, <span class="elsevierStyleItalic">DMD</span>, <span class="elsevierStyleItalic">DYSF</span>, <span class="elsevierStyleItalic">EMD</span>, <span class="elsevierStyleItalic">FHL1</span>, <span class="elsevierStyleItalic">LMNA</span>, <span class="elsevierStyleItalic">SYNE1</span>, and <span class="elsevierStyleItalic">SYNE2</span>) detected no pathogenic mutations. A subsequent sequencing study of 22 genes, including <span class="elsevierStyleItalic">TTN</span>, revealed loss of heterozygosity, affecting at least exons 32 to 364 of the gene. The study detected the c.86581T>A (p.Trp28861Arg) <span class="elsevierStyleItalic">TTN</span> variant in homozygosis. Cosegregation analysis detected the same variant in heterozygosis in both parents.</p><p id="par0035" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">TTN</span> mutations have been associated with various muscle diseases, cardiomyopathies, or a combination of both. The first mutation (an 11-bp insertion/deletion) was reported in 2002, and was called FINmaj.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> A dominant missense mutation in exon 364 (c.107840T>A p.Ile35947Asn) was subsequently detected in a Belgian family.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> In 2008, Hackman et al.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> described 3 novel mutations in 2 Spanish families and 2 French families (2 deletions, g.292998delT and g.293376delA) and a nonsense mutation (g.293379C>T [p.Q33396X]). A more recent study describes the phenotype of an Italian family with TMD and a new heterozygous mutation, g.293326A>C, which predicts the amino acid substitution p.His33378Pro.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Algahtani et al.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> report the heterozygous nonsense mutation c.85652C>G (p.Pro28551Arg) in a Saudi patient with bilateral facial weakness.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We describe a novel variant of <span class="elsevierStyleItalic">TTN</span> in homozygosis in a Spanish patient with TMD and cardiomyopathy. The patient presented nucleotide variant c.86581T>A (p.Trp28861Arg), apparently in homozygosis, in exon 341 of <span class="elsevierStyleItalic">TTN</span>. This variant causes the substitution of tryptophan for arginine at position 28861 of the polypeptide chain; these 2 amino acids have moderately different physicochemical properties. The change is located in a residue of the fibronectin type III domain, a conserved protein domain widely found in animal proteins. This variant has not previously been described in the literature, nor is it included in the ClinVar, dbSNP, ExAC, or ESP databases.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The presence of weakness affecting the muscles of the anterior compartment of the lower limbs suggests that this novel homozygous variant of <span class="elsevierStyleItalic">TTN</span> is pathogenic, and potentially involved in the pathogenesis of TMD and cardiomyopathy.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lopez-Bravo A, Roche-Bueno JC, Romera-López A, Larrode-Pellicer P. Una nueva variante en el gen de la titina en un paciente con miopatía distal de miembros inferiores y miocardiopatía dilatada. Neurología. 2021;36:721–723.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1612 "Ancho" => 1007 "Tamanyo" => 65046 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Muscle MRI (axial plane, T2-weighted sequence): atrophy with fat replacement in the extensor muscles of the lower limbs.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac titin: structure, functions and role in disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.M. LeWinter" 1 => "Y. Wu" 2 => "S. Labeit" 3 => "H. Granzier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cca.2006.06.035" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta." "fecha" => "2007" "volumen" => "375" "paginaInicial" => "1" "paginaFinal" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16904093" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increasing role of titin mutations in neuromuscular disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Savarese" 1 => "J. Sarparanta" 2 => "A. Vihola" 3 => "B. Udd" 4 => "P. Hackman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3233/JND-160158" "Revista" => array:6 [ "tituloSerie" => "J Neuromuscul Dis." "fecha" => "2016" "volumen" => "3" "paginaInicial" => "293" "paginaFinal" => "308" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27854229" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tibial muscular dystrophy. Late adult-onset distal myopathy in 66 Finnish patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. Udd" 1 => "J. Partanen" 2 => "P. Halonen" 3 => "B. Falck" 4 => "L. Hakamies" 5 => "H. Heikkila" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archneur.1993.00540060044015" "Revista" => array:6 [ "tituloSerie" => "Arch Neurol." "fecha" => "1993" "volumen" => "50" "paginaInicial" => "604" "paginaFinal" => "608" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8503797" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Truncating mutations in C-terminal titin may cause more severe tibial muscular dystrophy (TMD)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Hackman" 1 => "S. Marchand" 2 => "J. Sarparanta" 3 => "A. Vihola" 4 => "I. Penisson-Besnier" 5 => "B. Eymard" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Neuromuscular Disord." "fecha" => "2008" "volumen" => "18" "paginaInicial" => "922" "paginaFinal" => "928" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tibial muscular dystrophy in a Belgian family" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.Y.K. Van den Bergh" 1 => "O. Bouquiaux" 2 => "C. Verellen" 3 => "S. Marchand" 4 => "I. Richard" 5 => "P. Hackman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ana.10647" "Revista" => array:6 [ "tituloSerie" => "Ann Neurol." "fecha" => "2003" "volumen" => "54" "paginaInicial" => "248" "paginaFinal" => "251" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12891679" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Hackman" 1 => "A. Vihola" 2 => "H. Haravuori" 3 => "S. Marchand" 4 => "J. Sarparanta" 5 => "J. De Seze" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/342380" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet." "fecha" => "2002" "volumen" => "71" "paginaInicial" => "492" "paginaFinal" => "500" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12145747" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The first Italian family with tibial muscular dystrophy caused by a novel titin mutation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Pollazzon" 1 => "T. Suominen" 2 => "S. Penttila" 3 => "A. Malandrini" 4 => "M.A. Car- luccio" 5 => "M. Mondelli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00415-009-5372-3" "Revista" => array:6 [ "tituloSerie" => "J Neurol." "fecha" => "2010" "volumen" => "257" "paginaInicial" => "575" "paginaFinal" => "579" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19911250" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A novel mutation in <span class="elsevierStyleItalic">TTN</span> gene in a Saudi patient with bilateral facial weakness and scapular winging" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Algahtani" 1 => "B. Shirah" 2 => "R. Algahtani" 3 => "M.H. Al-Qahtani" 4 => "A.A. Abdulkareem" 5 => "M.I. Naseer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5582/irdr.2019.01052" "Revista" => array:6 [ "tituloSerie" => "Intractable Rare Dis Res." "fecha" => "2019" "volumen" => "8" "paginaInicial" => "142" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31218166" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735808/0000003600000009/v1_202110290547/S2173580821001085/v1_202110290547/en/main.assets" "Apartado" => array:4 [ "identificador" => "9409" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735808/0000003600000009/v1_202110290547/S2173580821001085/v1_202110290547/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580821001085?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 1 | 9 |
| 2024 October | 15 | 4 | 19 |
| 2024 September | 58 | 5 | 63 |
| 2024 August | 33 | 3 | 36 |
| 2024 July | 28 | 6 | 34 |
| 2024 June | 33 | 7 | 40 |
| 2024 May | 18 | 3 | 21 |
| 2024 April | 27 | 3 | 30 |
| 2024 March | 34 | 5 | 39 |
| 2024 February | 56 | 1 | 57 |
| 2024 January | 47 | 2 | 49 |
| 2023 December | 41 | 9 | 50 |
| 2023 November | 54 | 15 | 69 |
| 2023 October | 60 | 11 | 71 |
| 2023 September | 22 | 4 | 26 |
| 2023 August | 24 | 8 | 32 |
| 2023 July | 32 | 4 | 36 |
| 2023 June | 28 | 6 | 34 |
| 2023 May | 43 | 5 | 48 |
| 2023 April | 62 | 1 | 63 |
| 2023 March | 41 | 3 | 44 |
| 2023 February | 48 | 4 | 52 |
| 2023 January | 29 | 5 | 34 |
| 2022 December | 15 | 4 | 19 |
| 2022 November | 36 | 8 | 44 |
| 2022 October | 25 | 7 | 32 |
| 2022 September | 28 | 12 | 40 |
| 2022 August | 28 | 10 | 38 |
| 2022 July | 23 | 11 | 34 |
| 2022 June | 16 | 11 | 27 |
| 2022 May | 18 | 6 | 24 |
| 2022 April | 26 | 12 | 38 |
| 2022 March | 25 | 7 | 32 |
| 2022 February | 87 | 11 | 98 |
| 2022 January | 62 | 9 | 71 |
| 2021 December | 43 | 14 | 57 |
| 2021 November | 23 | 14 | 37 |
| 2021 October | 4 | 8 | 12 |
| 2021 September | 0 | 4 | 4 |
| 2021 August | 0 | 6 | 6 |
| 2021 July | 0 | 3 | 3 |
Show all
