Novel SCN5A mutation leading either to isolated cardiac conduction defect or Brugada syndrome in a large French family

Florence Kyndt, Vincent Probst, Franck Potet, Sophie Demolombe, Jean Christophe Chevallier, Isabelle Baro, Jean Paul Moisan, Pierre Boisseau, Jean Jacques Schott, Denis Escande, Hervé Le Marec*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

337 Scopus citations


Background - The SCN5A gene encoding the human cardiac sodium channel α subunit plays a key role in cardiac electrophysiology. Mutations in SCN5A lead to a large spectrum of phenotypes, including long-QT syndrome, Brugada syndrome, and isolated progressive cardiac conduction defect (Lenègre disease). Methods and Results - In the present study, we report the identification of a novel single SCN5A 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 SCN5A 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 SCN5A showed no detectable Na+ current but normal protein trafficking. Conclusions - We conclude that the same mutation in the SCN5A 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 SCN5A mutation.

Original languageEnglish (US)
Pages (from-to)3081-3086
Number of pages6
Issue number25
StatePublished - Dec 18 2001


  • Arrhythmia
  • Bundle-branch block
  • Fibrillation
  • Genetics
  • Heart block

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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