{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:46:15Z","timestamp":1789145175565,"version":"build-2803163510"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["C\u00e1tedras 1703"],"award-info":[{"award-number":["C\u00e1tedras 1703"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["SALUD-2010-01-140259"],"award-info":[{"award-number":["SALUD-2010-01-140259"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["FOSISS 261670"],"award-info":[{"award-number":["FOSISS 261670"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["Fellowship 719803"],"award-info":[{"award-number":["Fellowship 719803"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Sodium voltage-gated channel \u03b1 subunit 5 (SCN5A)-mutations may cause an array of arrhythmogenic syndromes most frequently as an autosomal dominant trait, with incomplete penetrance, variable expressivity and male predominance. In the present study, we retrospectively describe a group of Mexican patients with SCN5A-disease causing variants in whom the onset of symptoms occurred in the pediatric age range. The study included 17 patients with clinical diagnosis of primary electrical disease, at least one SCN5A pathogenic or likely pathogenic mutation and age of onset &lt;18 years, and all available first- and second-degree relatives. Fifteen patients (88.2%) were male, and sixteen independent variants were found (twelve missense, three truncating and one complex inframe deletion\/insertion). The frequency of compound heterozygosity was remarkably high (3\/17, 17.6%), with early childhood onset and severe disease. Overall, 70.6% of pediatric patients presented with overlap syndrome, 11.8% with isolated sick sinus syndrome, 11.8% with isolated Brugada syndrome (BrS) and 5.9% with isolated type 3 long QT syndrome (LQTS). A total of 24\/45 SCN5A mutation carriers were affected (overall penetrance 53.3%), and penetrance was higher in males (63.3%, 19 affected\/30 mutation carriers) than in females (33.3%, 5 affected\/15 carriers). In conclusion, pediatric patients with SCNA-disease causing variants presented mainly as overlap syndrome, with predominant loss-of-function phenotypes of sick sinus syndrome (SSS), progressive cardiac conduction disease (PCCD) and ventricular arrhythmias.<\/jats:p>","DOI":"10.3390\/genes13010016","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T02:01:19Z","timestamp":1640224879000},"page":"16","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Clinical Spectrum of SCN5A Channelopathy in Children with Primary Electrical Disease and Structurally Normal Hearts"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4450-7690","authenticated-orcid":false,"given":"Teresa","family":"Villarreal-Molina","sequence":"first","affiliation":[{"name":"Laboratory of Cardiovascular Genomics, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Paola","family":"Garc\u00eda-Ord\u00f3\u00f1ez","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Genomics, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9732-8755","authenticated-orcid":false,"given":"\u00c1lvaro E.","family":"Reyes-Quintero","sequence":"additional","affiliation":[{"name":"Departament of Electrocardiology, National Institute of Cardiology \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6049-0430","authenticated-orcid":false,"given":"Mayra","family":"Dom\u00ednguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Genomics, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5129-8108","authenticated-orcid":false,"given":"Leonor","family":"Jacobo-Albavera","sequence":"additional","affiliation":[{"name":"Laboratory of Cardiovascular Genomics, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santiago","family":"Nava","sequence":"additional","affiliation":[{"name":"Departament of Electrocardiology, National Institute of Cardiology \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Carnevale","sequence":"additional","affiliation":[{"name":"Laboratory of Mendelian Diseases, National Institute of Genomic Medicine, Mexico City 14610, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argelia","family":"Medeiros-Domingo","sequence":"additional","affiliation":[{"name":"Swiss DNAlysis, Cardiogenetics, 8600 D\u00fcbendorf, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Iturralde","sequence":"additional","affiliation":[{"name":"Departament of Electrocardiology, National Institute of Cardiology \u201cIgnacio Ch\u00e1vez\u201d, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.gene.2015.08.062","article-title":"The cardiac sodium channel gene SCN5A and its gene product NaV1.5: Role in physiology and pathophysiology","volume":"573","author":"Veerman","year":"2015","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.bbamcr.2012.10.026","article-title":"Cardiac sodium channel NaV1.5 distribution in myocytes via interacting proteins: The multiple pool model","volume":"1833","author":"Shy","year":"2013","journal-title":"Biochim. 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