{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:36:59Z","timestamp":1791142619051,"version":"4.1.0"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"25","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2001,12,17]]},"abstract":"<jats:p><jats:bold><jats:italic><jats:bold><jats:italic>Background<\/jats:italic>\u2014<\/jats:bold><\/jats:italic><\/jats:bold>The<jats:italic>SCN5A<\/jats:italic>gene encoding the human cardiac sodium channel \u03b1 subunit plays a key role in cardiac electrophysiology. Mutations in<jats:italic>SCN5A<\/jats:italic>lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lene\u0300gre disease).<\/jats:p><jats:p><jats:bold><jats:italic><jats:bold><jats:italic>Methods and Results<\/jats:italic>\u2014<\/jats:bold><\/jats:italic><\/jats:bold>In the present study, we report the identification of a novel single<jats:italic>SCN5A<\/jats:italic>missense mutation causing either Brugada syndrome or an isolated cardiac conduction defect in the same family. A G-to-T mutation at position 4372 was identified by direct sequencing and was predicted to change a glycine for an arginine (G1406R) between the DIII-S5 and DIII-S6 domain of the sodium channel protein. Among 45 family members, 13 were carrying the G1406R<jats:italic>SCN5A<\/jats:italic>mutation. Four individuals from 2 family collateral branches showed typical Brugada phenotypes, including ST-segment elevation in the right precordial leads and right bundle branch block. One symptomatic patient with the Brugada phenotype required implantation of a cardioverter-defibrillator. Seven individuals from 3 other family collateral branches had isolated cardiac conduction defects but no Brugada phenotype. Three flecainide test were negative. One patient with an isolated cardiac conduction defect had an episode of syncope and required pacemaker implantation. An expression study of the G1406R-mutated<jats:italic>SCN5A<\/jats:italic>showed no detectable Na<jats:sup>+<\/jats:sup>current but normal protein trafficking.<\/jats:p><jats:p><jats:bold><jats:italic><jats:bold><jats:italic>Conclusions<\/jats:italic>\u2014<\/jats:bold><\/jats:italic><\/jats:bold>We conclude that the same mutation in the<jats:italic>SCN5A<\/jats:italic>gene can lead either to Brugada syndrome or to an isolated cardiac conduction defect. Our findings suggest that modifier gene(s) may influence the phenotypic consequences of a<jats:italic>SCN5A<\/jats:italic>mutation.<\/jats:p>","DOI":"10.1161\/hc5001.100834","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:31:09Z","timestamp":1191004269000},"page":"3081-3086","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":297,"title":["Novel<i>SCN5A<\/i>Mutation Leading Either to Isolated Cardiac Conduction Defect or Brugada Syndrome in a Large French Family"],"prefix":"10.1161","volume":"104","author":[{"given":"Florence","family":"Kyndt","sequence":"first","affiliation":[{"name":"From the Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Mole\u0301culaires, INSERM U533, Ho\u0302pital Hotel-Dieu, the Laboratoire de Ge\u0301ne\u0301tique Mole\u0301culaire, Ho\u0302pital Hotel-Dieu and the De\u0301partement de Cardiologie, Ho\u0302pital G&amp;R Laennec, Nantes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Probst","sequence":"additional","affiliation":[{"name":"From the Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Mole\u0301culaires, INSERM U533, Ho\u0302pital Hotel-Dieu, the Laboratoire de Ge\u0301ne\u0301tique Mole\u0301culaire, Ho\u0302pital Hotel-Dieu and the De\u0301partement de Cardiologie, Ho\u0302pital G&amp;R Laennec, Nantes, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Potet","sequence":"additional","affiliation":[{"name":"From the Laboratoire de Physiopathologie et de Pharmacologie Cellulaires et Mole\u0301culaires, INSERM U533, Ho\u0302pital Hotel-Dieu, the Laboratoire de Ge\u0301ne\u0301tique Mole\u0301culaire, Ho\u0302pital Hotel-Dieu and the De\u0301partement de Cardiologie, Ho\u0302pital G&amp;R Laennec, Nantes, 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