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(A, B) Some large or small red spots were observed on the eyelids; (C) Red spots were also observed on the tongue; (D, E) Several large red or pink spots were observed on the palate and on the nasal cavity by nasal endoscopy, respectively.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Fang Chen, Mengxue Yang, Zhong Wen, Chaosheng Yu" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Fang" "apellidos" => "Chen" ] 1 => array:2 [ "nombre" => "Mengxue" "apellidos" => "Yang" ] 2 => array:2 [ "nombre" => "Zhong" "apellidos" => "Wen" ] 3 => array:2 [ "nombre" => "Chaosheng" "apellidos" => "Yu" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020621006112" "doi" => "10.1016/j.medcle.2021.07.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621006112?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775321005194?idApp=UINPBA00004N" "url" => "/00257753/0000015700000011/v1_202111210516/S0025775321005194/v1_202111210516/en/main.assets" ] ] "itemSiguiente" => array:18 [ "pii" => "S2387020621006276" "issn" => "23870206" "doi" => "10.1016/j.medcle.2020.11.037" "estado" => "S300" "fechaPublicacion" => "2021-12-10" "aid" => "5510" "copyright" => "Elsevier España, S.L.U." 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"documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2021;157:535-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial article</span>" "titulo" => "Transcatheter valve implantation in 2021: A reality whose limits we still do not know" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "535" "paginaFinal" => "536" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Los implantes valvulares transcatéter en el 2021: una realidad cuyos límites aún desconocemos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Pedro Luis Cepas-Guillén, Manel Sabate" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Pedro Luis" "apellidos" => "Cepas-Guillén" ] 1 => array:2 [ "nombre" => "Manel" "apellidos" => "Sabate" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S002577532100508X" "doi" => "10.1016/j.medcli.2021.09.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002577532100508X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621005945?idApp=UINPBA00004N" "url" => "/23870206/0000015700000011/v1_202112030828/S2387020621005945/v1_202112030828/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Clinical report</span>" "titulo" => "Identification of a novel <span class="elsevierStyleItalic">ENG</span> gene mutation (c.1550_1551dupTG, p.S518*) in a Chinese family with hereditary hemorrhagic telangiectasia" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "537" "paginaFinal" => "541" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Fang Chen, Mengxue Yang, Zhong Wen, Chaosheng Yu" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Fang" "apellidos" => "Chen" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 1 => array:3 [ "nombre" => "Mengxue" "apellidos" => "Yang" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 2 => array:4 [ "nombre" => "Zhong" "apellidos" => "Wen" "email" => array:1 [ 0 => "wenzhong60@163.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 3 => array:4 [ "nombre" => "Chaosheng" "apellidos" => "Yu" "email" => array:1 [ 0 => "ycs_9982@163.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Otorhinolaryngology-Head and Neck Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, China" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Otorhinolaryngology-Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding authors." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Identificación de una nueva mutación del gen <span class="elsevierStyleItalic">ENG</span> (c.1550_1551dupTG, p.S518 *) en una familia china con telangiectasia hemorrágica hereditaria" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1447 "Ancho" => 3000 "Tamanyo" => 1012263 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">heterozygous variant [c.1550_1551dupTG (p.S518*)] in ENG gene.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu disease) is an autosomal dominant genetic disease characterized by clinically significant vascular malformations (VMs) of skin and mucous membranes of the nose and gastrointestinal (GI) tract as well as the liver, lung, and/or central nervous system.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> The estimated prevalence of HHT was approximately 1 in 5000,<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> whereas it is underdiagnosed, and a long diagnostic delay is common.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> It is thus very important to diagnose HHT early through appropriate screening and preventive treatment of a patient and their affected family members. The most common symptom of HHT is epistaxis, which has an age-related expression as does the appearance of the typical telangiectasia.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The Curaçao criteria that published in 2000 are the consensus clinical diagnostic criteria for HHT.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Although HHT can be clinically diagnosed by using the Curaçao criteria, the International HHT Guidelines also recommended genetic testing for HHT diagnosis, primarily for asymptomatic persons with a family history of HHT.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Since families with the same mutation exhibit considerable phenotypic variation, it is best to conduct appropriate diagnosis, screening, and local and/or systemic management of the lesion through a multidisciplinary approach to achieve optimal treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Mutations in four genes (<span class="elsevierStyleItalic">ENG</span>, <span class="elsevierStyleItalic">ACVRL1/ALK1</span>, <span class="elsevierStyleItalic">SMAD4/SMAD4</span>, and <span class="elsevierStyleItalic">GDF2</span>) have been described in HHT.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In most cases, HHT is caused by a mutation in 1 of 2 major genes: <span class="elsevierStyleItalic">ENG</span> (HHT 1) (OMIM #187300) and <span class="elsevierStyleItalic">ACVRL1</span> (HHT 2) (OMIM #600736).<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In 1994, <span class="elsevierStyleItalic">ENG</span> with a chromosomal location of 9q34.11 that encodes for endoglin was the first gene identified in which mutations resulted in HHT. Endoglin is a cell-surface glycoprotein that functions as part of the transforming growth factor beta (TGF-β) signaling complex that serves an important role in angiogenesis and vascular remodeling.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> In addition, Endoglin is also an auxiliary co-receptor at the endothelial cell surface that promotes BMP9 signaling through the activin receptor-like kinase 1 (ALK1) encoded by <span class="elsevierStyleItalic">ACVRL1</span>.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Previous study has reported that defects in the <span class="elsevierStyleItalic">ACVRL1</span> gene on chromosome 12q13 were recognized to cause HHT.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Together with endoglin, ALK1 acts as a cell-surface receptor for the TGF-β/BMP signaling pathways, which is important in the regulation of angiogenesis.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In this study, we report on a case of HHT in a Chinese family with a novel heterozygous variation c.1550_1551dupTG (p.S518*) in <span class="elsevierStyleItalic">ENG</span> gene.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Case presentation</span><p id="par0020" class="elsevierStylePara elsevierViewall">A 60-year-old Chinese man (II-13 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) admitted to the hospital due to spontaneous and recurrent epistaxis. He had experienced recurrent epistaxis 20 years ago and did not receive regular treatment until 2015. Prior to admission, the patient had been admitted to a local hospital for nasal packing surgery due to “nosebleed” in November 2015. He was then transferred to a higher level hospital for a nasal embolization procedure because of the poor effect of nasal congestion. In the past month, the patient's symptoms have worsened, and the amount of bleeding is about 50<span class="elsevierStyleHsp" style=""></span>mL each time.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">On visual inspection, the patient exhibited multiple red or pink spots reflecting telangiectases on the eyelids, tongue, palate and nasal cavity (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Chest radiograph and echocardiography did not show any obvious abnormalities. The main laboratory results were as follows: red blood cell count (2.93<span class="elsevierStyleHsp" style=""></span>T/L) and hemoglobin concentration (93<span class="elsevierStyleHsp" style=""></span>g/L) were lower than normal reference interval, while prothrombin time (15.9<span class="elsevierStyleHsp" style=""></span>s), partial thromboplastin time (48<span class="elsevierStyleHsp" style=""></span>s) and fibrinogen (5.09<span class="elsevierStyleHsp" style=""></span>g/L) were higher than normal reference interval. No obvious abnormalities in liver and kidney function, urine and stool routine, CT of sinuses and nasopharynx prompts sinusitis, nasal septum deviation. These findings indicated that the patient has severe anemia and coagulation system disorder.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The patient's family history revealed that his father (I-1 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), brothers (II-3 and II-9 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), sister (II-8 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and nephews (III-8, III-9 and III-16 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) also had frequent epistaxis. His father (I-1 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), brother (II-3 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and sister (II-8 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) had died due to nose bleeding. His brother (II-9 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) had repeated nosebleeds for 15 years without finding the cause, and was admitted to the hospital for blood transfusion for several times because of anemia. His daughter (III-15 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) had clinical manifestations of repeated epistaxis for more than 10 years, about once a month, worsened during menstruation, and exhibited telangiectasia in bilateral nasal cavity by nasal endoscopy (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Therefore, whole exome gene sequencings of the patient and his son, daughter were performed and we identified a novel heterozygous variant [c.1550_1551dupTG (p.S518*)] in <span class="elsevierStyleItalic">ENG</span> gene in the patient's daughter, which had been inherited from the heterozygous patient (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). The first-generation sequencing method is used to detect and analyze the relevant site-specific mutations of the patient's son and no <span class="elsevierStyleItalic">ENG</span> gene related mutation was found. Based on these findings, we ultimately diagnosed HHT in the patient and his daughter in accordance with Curaçao's diagnostic criteria.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">HHT is diagnosed clinically by (1) spontaneous and recurrent epistaxis; (2) multiple telangiectases of the lips, oral cavity, fingers, and nose; (3) visceral AVM (particularly in the lungs, liver, and brain) and (4) a family history of HHT according to the Curaçao criteria.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> As our patient met two of the clinical criteria for HHT at his initial visit, we mad the diagnosis of possible HHT but not definite HHT. According to his family history, the patient's father, brothers, sister and daughter were highly suspected of having HHT. If the patient's brother (II-9 in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) or daughter were diagnosed with HHT, our patient and his family members would be diagnosed as having definite HHT. Our patient's case was thus definite HHT because the presence of his daughter with HHT was confirmed by genetic testing.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In the genetic test, high-precision clinical penetrance PLUS detection and analysis were performed on the patient, his son and daughter at the same time, and the <span class="elsevierStyleItalic">ENG</span> heterozygous variant c.1550_1551dupTG (p.S518*) was detected. The sequencing data showed that this mutation was inherited from the patient (heterozygous state). So far, this variation has not been reported in relevant clinical cases and in our reference population gene database. The <span class="elsevierStyleItalic">ENG</span> heterozygous variant c.1550_1551dupTG (p.S518*) is a likely pathogenic variant, which is classified as “Class 2-May Cause Disease” according to the American ACMG Variant Classification Guidelines (PMID: 25741868).<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> This mutation is a frameshift mutation, which is predicted to cause the amino acid termination code appearing early in protein synthesis. The <span class="elsevierStyleItalic">ENG</span> gene encodes endothelial factor, which participates in the formation of the TGF-β receptor complex and plays an important role in the process of regulating blood vessel formation (PMID: 21737454). The <span class="elsevierStyleItalic">ENG</span> gene-related disease is hereditary hemorrhagic telangiectasia (HHT), which is inherited in an autosomal dominant manner. The clinical feature of HHT is multiple arteriovenous malformations, which are mainly manifested as spontaneous and recurrent epistaxis, with an average age of onset of 12 years; after epistaxis, lip, tongue, buccal mucosa, face, cheek, fingers and other parts may appear dilation of capillaries; severe acute bleeding may occur when arteriovenous malformations occur in the lungs, liver, and brain; some patients will have gastrointestinal bleeding after the age of 50 (PMID: 20301525). Therefore, it is necessary to further evaluate the clinical relevance based on the clinical manifestations, vascular imaging examinations, and family genetic analysis of the submitter and related paternal relatives.</p><p id="par0045" class="elsevierStylePara elsevierViewall">There is no evidence that the patient's son has related mutations in the <span class="elsevierStyleItalic">ENG</span> gene. Although this result can be considered to reduce the risk of genetic diseases related to the mutation, the above results cannot completely rule out the possibility of the patient's son suffering from related diseases. The test results are based on our current understanding of genes related to genetic diseases, and the possibility of other unknown pathogenic variants outside the scope of the tested genes cannot be ruled out. Thus, we highly recommended that relatives of the paternal line undergo corresponding site-specific mutation testing to assess the source of the mutation, disease relevance and genetic risk.</p><p id="par0050" class="elsevierStylePara elsevierViewall">In examining the family tree, we identified 9 other affected relatives including the patient's father, brothers, sister, daughter and nephews. Since the <span class="elsevierStyleItalic">ENG</span> heterozygous variant c.1550_1551dupTG (p.S518*) inherited from the patient (heterozygous state) was detected from his daughter, we speculate that the mutation was passed in heterozygous form from his father. Additionally, the patient and his family members exhibited severe clinical symptoms, among which three family members had died due to nose bleeding and one member had experienced symptomatic anaemia requiring blood transfusions. Although these members did not undergo corresponding site-specific mutation testing, we predict that the novel <span class="elsevierStyleItalic">ENG</span> heterozygous variant c.1550_1551dupTG (p.S518*) in our cases with HHT may play an important role on the severe symptoms because of complete loss of <span class="elsevierStyleItalic">ENG</span> function. However, further case follow-up and functional studies should be conducted to confirm these mechanismal hypotheses.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, the patient and his daughter were confirmed to have heterozygous <span class="elsevierStyleItalic">ENG</span>-related HHT by genetic testing and a novel c.1550_1551dupTG (p.S518*) mutation in <span class="elsevierStyleItalic">ENG</span> was identified. In addition, the heterozygous variant has never been reported, constituting an important new finding for researchers and clinicians studying HHT. The findings and their implications should be discussed in the broadest context possible. Future research directions may also be highlighted.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Informed consent statement</span><p id="par0060" class="elsevierStylePara elsevierViewall">Informed consent was obtained from all subjects involved in the study.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflicts of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1621008" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1447536" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1621007" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedente" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1447537" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Case presentation" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Informed consent statement" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflicts of interest" ] 9 => array:2 [ "identificador" => "xack571964" "titulo" => "Acknowledgments" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-04-14" "fechaAceptado" => "2021-07-07" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1447536" "palabras" => array:5 [ 0 => "<span class="elsevierStyleItalic">ENG</span>" 1 => "Hereditary hemorrhagic telangiectasia" 2 => "Epistaxis" 3 => "Missense mutation" 4 => "Osler-Weber-Rendu disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1447537" "palabras" => array:5 [ 0 => "EN<span class="elsevierStyleItalic">G</span>" 1 => "Telangiectasia hemorrágica hereditaria" 2 => "Epistaxis" 3 => "Mutación sin sentido" 4 => "Enfermedad de Osler-Weber-Rendu" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">It is very important to diagnose Hereditary hemorrhagic telangiectasia (HHT) early through appropriate screening and preventive treatment of a patient and their affected family members. This study aimed to report on a case of a Chinese family with heterozygous <span class="elsevierStyleItalic">ENG</span>-related HHT.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Gene mutations were identified by whole-exome sequencing and physical examination were conducted to reveal the clinical symptoms.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Physical examination revealed symptomatic anaemia, coagulation system disorder and multiple red or pink spots reflecting telangiectases on the eyelids, tongue, palate and nasal cavity. Nine other affected relatives were identified in examining his family tree, among which three family members had died due to nose bleeding and one member presented symptomatic anaemia requiring blood transfusions. A novel heterozygous variation c.1550_1551dupTG (p.S518*) in <span class="elsevierStyleItalic">ENG</span> gene was identified.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The patient and his daughter were confirmed to have heterozygous <span class="elsevierStyleItalic">ENG</span>-related HHT and the novel ENG heterozygous variant may play an important role on the severe symptoms of HHT. However, further case follow-up and functional studies should be conducted to confirm these mechanismal hypotheses.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedente</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El diagnóstico temprano de telangiectasia hemorrágica hereditaria (HHT) es muy relevante tanto para el propio paciente como para sus familiares afectados ya que permite un tratamiento preventivo. El objetivo de este estudio es presentar una familia china con HHT heterocigótica relacionada con una mutación en el gen <span class="elsevierStyleItalic">ENG</span>.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se llevó a cabo un estudio clínico y se identificaron mutaciones genéticas mediante secuenciación del exoma completo.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se detectaron anemia sintomática, trastornos de la coagulación y múltiples telangiectasias en párpados, lengua, paladar y cavidad nasal. Al examinar el árbol genealógico, se detectaron otros nueve familiares afectados, tres de los cuales habían fallecido por hemorragia nasal y uno presentaba anemia sintomática que había requerido transfusiones de sangre. Se identificó una nueva variación heterocigótica c.1550_1551dupTG (p.S518 *) en el gen <span class="elsevierStyleItalic">ENG</span>.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se confirmó que el paciente y su hija tenían HHT heterocigótica relacionada con el gen <span class="elsevierStyleItalic">ENG</span>. La nueva variante heterocigótica <span class="elsevierStyleItalic">ENG</span> puede desempeñar un papel relevante en la gravedad de los síntomas de la HHT, aunque se precisan nuevos estudios funcionales y de seguimiento de casos para confirmar dicha hipótesis.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedente" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">These authors contributes equally to this work.</p>" "identificador" => "fn0005" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 853 "Ancho" => 2167 "Tamanyo" => 66021 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">The family tree with male in <elsevierMultimedia ident="202112030829422081"></elsevierMultimedia>, female in <elsevierMultimedia ident="202112030829422082"></elsevierMultimedia>, epistaxis in black is shown. The proband patient is indicated by a black-filled square and arrow.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1406 "Ancho" => 1750 "Tamanyo" => 217595 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Typical images of the patient's telangiectasias. (A, B) Some large or small red spots were observed on the eyelids; (C) Red spots were also observed on the tongue; (D, E) Several large red or pink spots were observed on the palate and on the nasal cavity by nasal endoscopy, respectively.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 724 "Ancho" => 1300 "Tamanyo" => 86055 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Red spots were observed on the nasal cavity of the daughter of the patient by nasal endoscopy. (A) Left side and (B) right side.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1447 "Ancho" => 3000 "Tamanyo" => 1012263 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">heterozygous variant [c.1550_1551dupTG (p.S518*)] in ENG gene.</p>" ] ] 4 => array:5 [ "identificador" => "202112030829422081" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 12 "Ancho" => 12 "Tamanyo" => 281 ] ] ] 5 => array:5 [ "identificador" => "202112030829422082" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx2.jpeg" "Alto" => 17 "Ancho" => 16 "Tamanyo" => 324 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and treatment of hereditary hemorrhagic telangiectasia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. 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We also thank the reviewers for their substantial revision of this article.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015700000011/v1_202112030828/S2387020621006112/v1_202112030828/en/main.assets" "Apartado" => array:4 [ "identificador" => "44145" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015700000011/v1_202112030828/S2387020621006112/v1_202112030828/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621006112?idApp=UINPBA00004N" ]
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Clinical report
Identification of a novel ENG gene mutation (c.1550_1551dupTG, p.S518*) in a Chinese family with hereditary hemorrhagic telangiectasia
Identificación de una nueva mutación del gen ENG (c.1550_1551dupTG, p.S518 *) en una familia china con telangiectasia hemorrágica hereditaria