Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Nav1.5 α-subunits

Jérôme Clatot (1) , Azza Ziyadeh-Isleem (2) , Svetlana Maugenre (2) , Isabelle Denjoy (3) , Haiyan Liu (4) , Gilles Dilanian (2) , Stéphane N. Hatem (1) , Isabelle Deschênes (4) , Alain Coulombe (2) , Pascale Guicheney (2) , Nathalie Neyroud (2)

1 Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires
2 Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [CHU Pitié-Salpétriêre]
3 Service de cardiologie (APHP-Hôpital Lariboisière)
4 MetroHealth Medical Center

Brugada syndrome (BrS) is an autosomal-inherited cardiac arrhythmia characterized by an ST-segment elevation in the right precordial leads of the electrocardiogram and an increased risk of syncope and sudden death. SCN5A, encoding the cardiac sodium channel Na(v)1.5, is the main gene involved in BrS. Despite the fact that several mutations have been reported in the N-terminus of Na(v)1.5, the functional role of this region remains unknown. We aimed to characterize two BrS N-terminal mutations, R104W and R121W, a construct where this region was deleted, ΔNter, and a construct where only this region was present, Nter.

Domaines: Cardiologie et système cardiovasculaire

Jérôme Clatot, Azza Ziyadeh-Isleem, Svetlana Maugenre, Isabelle Denjoy, Haiyan Liu, et al.. Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Nav1.5 α-subunits. Cardiovascular Research, 2012, 96 (1), pp.53-63. ⟨10.1093/cvr/cvs211⟩. ⟨hal-02330941⟩