Europace Advance Access originally published online on December 21, 2007
Europace 2008 10(1):79-85; doi:10.1093/europace/eum271
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BRUGADA SYNDROME
The occurrence of Brugada syndrome and isolated cardiac conductive disease in the same family could be due to a single SCN5A mutation or to the accidental association of both diseases
1 INSERM ERI 12, Amiens, France; 2 Department of Cardiology, Amiens-Picardie University Hospital, 80054 Amiens Cedex 1, France; 3 Research Center, Laval Hospital and Department of Medicine, Laval University, Québec, Canada; 4 INSERM U582, Institut de Myologie, IFR 14, Pitié-Salpêtrière Hospital, Paris, France; 5 Pierre et Marie Curie University, Paris, France; 6 UF Cardiogénétique et Myogénétique, Service de Biochimie B, Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Paris, France; 7 Department of Cardiology, Lariboisière Hospital, Paris, France
Aims: The distinct cardiac arrhythmia diseases, Brugada syndrome (BS) and isolated cardiac conduction disease (ICCD) are caused by heterozygous mutations in the SCN5A gene. Previous studies have demonstrated an intriguing association between ICCD and BS with the same mutation in the SCN5A gene.
Methods and results: The proband of a multigenerational family presented BS and a familial history of sudden death. We performed clinical evaluations in family members including drug testing and screening for SCN5A mutations. Based on electrocardiogram features, we identified four individuals with BS, two with ICCD and one compatible with both. For five individuals, one with BS and ICCD, three with BS and one with ICCD, we characterized a heterozygous C- to T- mutation at position 4313 (P1438L) in the SCN5A gene. Expression studies of the P1438L mutation showed non-functional channels. The proband’s father with the BS phenotype was not a carrier of the new SCN5A mutation.
Conclusion: We report the case of a family with BS and/or ICCD and describe a novel mutation, the P1438L SCN5A mutation. In this family, the occurrence of BS and ICCD could be due to this single mutation but also to the accidental association of both diseases.
Key Words: Arrhythmia, Cardiac conduction disease, Genetics
* Corresponding author. Tel: +33 3 22 45 58 75; fax: +33 3 22 45 56 61.E-mail address: hermida.jean-sylvain{at}chu-amiens.fr
Manuscript submitted 10 September 2007. Accepted after revision 15 November 2007.