{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:55:55Z","timestamp":1784566555330,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RHL135767A"],"award-info":[{"award-number":["RHL135767A"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Long <jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content> syndrome (LQT) is a pro\u2010arrhythmogenic condition with life\u2010threatening complications. Fifteen genes have been associated with congenital <jats:styled-content style=\"fixed-case\">LQT<\/jats:styled-content>, however, the genetic causes remain unknown in more than 20% of cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Eighteen patients with history of palpitations, pre\u2010syncope, syncope and prolonged <jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content> were referred to the Yale Cardiovascular Genetics Program. All subjects underwent whole\u2010exome sequencing (<jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content>) followed by confirmatory Sanger sequencing. Mutation burden analysis was carried out using <jats:styled-content style=\"fixed-case\">WES<\/jats:styled-content> data from 16 subjects with no identifiable cause of <jats:styled-content style=\"fixed-case\">LQT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Deleterious and novel <jats:italic><jats:styled-content style=\"fixed-case\">SCN10A<\/jats:styled-content><\/jats:italic> mutations were identified in 3 of the 16 patients (19%) with idiopathic <jats:styled-content style=\"fixed-case\">LQT<\/jats:styled-content>. These included 2 frameshifts and 1 missense variants (p.G810fs, p.<jats:styled-content style=\"fixed-case\">R1259Q<\/jats:styled-content>, and p.P1877fs). Further analysis identified 2 damaging <jats:italic><jats:styled-content style=\"fixed-case\">SCN10A<\/jats:styled-content><\/jats:italic> mutations with allele frequencies of approximately 0.2% (p.<jats:styled-content style=\"fixed-case\">R14L<\/jats:styled-content> and p.<jats:styled-content style=\"fixed-case\">R1268Q<\/jats:styled-content>) in 2 independent cases. None of the <jats:italic><jats:styled-content style=\"fixed-case\">SCN10A<\/jats:styled-content><\/jats:italic> mutation carriers had mutations in known arrhythmia genes. Damaging <jats:italic><jats:styled-content style=\"fixed-case\">SCN10A<\/jats:styled-content><\/jats:italic> mutations (p.<jats:styled-content style=\"fixed-case\">R209H<\/jats:styled-content> and p.<jats:styled-content style=\"fixed-case\">R485C<\/jats:styled-content>) were also identified in the 2 subjects on <jats:styled-content style=\"fixed-case\">QT<\/jats:styled-content> prolonging medications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings implicate <jats:italic><jats:styled-content style=\"fixed-case\">SCN10A<\/jats:styled-content><\/jats:italic> in <jats:styled-content style=\"fixed-case\">LQT<\/jats:styled-content>. The presence of frameshift mutations suggests loss\u2010of\u2010function as the underlying disease mechanism. The common association with <jats:styled-content style=\"fixed-case\">atrial fibrillation<\/jats:styled-content> suggests a unique mechanism of disease for this <jats:styled-content style=\"fixed-case\">LQT<\/jats:styled-content> gene.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cge.13036","type":"journal-article","created":{"date-parts":[[2017,4,13]],"date-time":"2017-04-13T16:10:09Z","timestamp":1492099809000},"page":"741-751","source":"Crossref","is-referenced-by-count":15,"title":["Deleterious protein\u2010altering mutations in the <i><scp>SCN10A<\/scp><\/i> voltage\u2010gated sodium channel gene are associated with prolonged <scp>QT<\/scp>"],"prefix":"10.1111","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5316-4875","authenticated-orcid":false,"given":"M.D.","family":"Abou Ziki","sequence":"first","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine Yale University School of Medicine  New Haven 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Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Jiang","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.G.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.A.","family":"Marieb","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal Medicine Yale University School of Medicine  New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Akar","sequence":"additional","affiliation":[{"name":"Section of Cardiovascular Medicine, Department of Internal 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