SCN5A Mutations and the role of genetic background in the pathophysiology of brugada syndrome

Vincent Probst, Arthur A M Wilde, Julien Barc, Frederic Sacher, Dominique Babuty, Philippe Mabo, Jacques Mansourati, Solena Le Scouarnec, Florence Kyndt, Cedric Le Caignec, Pascale Guicheney, Laetitia Gouas, Juliette Albuisson, Paola G. Meregalli, Hervé Le Marec, Hanno L. Tan, Jean Jacques Schott

Research output: Contribution to journalArticlepeer-review


Background-Mutations in SCN5A are identified in =20% to 30% of probands affected by Brugada syndrome (BrS). However, in familial studies, the relationship between SCN5A mutations and BrS remains poorly understood. The aim of this study was to investigate the association of SCN5A mutations and BrS in a group of large genotyped families. Methods and Results-Families were included if at least 5 family members were carriers of the SCN5A mutation, which was identified in the proband. Thirteen large families composed of 115 mutation carriers were studied. The signature type I ECG was present in 54 mutation carriers (BrS-ECG-; 47%). In 5 families, we found 8 individuals affected by BrS but with a negative genotype (mutation-negative BrS-ECG-). Among these 8 mutation-negative BrS-ECG- individuals, 3, belonging to 3 different families, had a spontaneous type I ECG, whereas 5 had a type I ECG only after the administration of sodium channel blockers. One of these 8 individuals had also experienced syncope. Mutation carriers had, on average, longer PR and QRS intervals than noncarriers, demonstrating that these mutations exerted functional effects. Conclusions-Our results suggest that SCN5A mutations are not directly causal to the occurrence of a BrS-ECG- and that genetic background may play a powerful role in the pathophysiology of BrS. These findings add further complexity to concepts regarding the causes of BrS, and are consistent with the emerging notion that the pathophysiology of BrS includes various elements beyond mutant sodium channels.

Original languageEnglish
Pages (from-to)552-557
Number of pages6
JournalCirculation: Cardiovascular Genetics
Issue number6
Publication statusPublished - Dec 2009


  • Arrhythmia
  • Brugada syndrome
  • Death, Sudden (If surviving, Use heart arrest)
  • Genetics
  • SCN5A
  • Tachyarrhythmias

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)
  • Genetics
  • Medicine(all)

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