SCN5A Variants as Genetic Arrhythmias Triggers for Familial Bileaflet Mitral Valve Prolapse

Hager Jaouadi (1) , Alexis Théron , Jérôme Hourdain , Hélène Martel , Karine Nguyen , Raja Habachi , Jean-Claude Deharo , Frédéric Collart , Jean-François Avierinos , Stéphane Zaffran (1)

1 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille

Mitral valve prolapse (MVP) is a common valvular heart defect with variable outcomes. Several studies reported MVP as an underestimated cause of life-threatening arrhythmias and sudden cardiac death (SCD), mostly in young adult women. Herein, we report a clinical and genetic investigation of a family with bileaflet MVP and a history of syncopes and resuscitated sudden cardiac death. Using family based whole exome sequencing, we identified two missense variants in the SCN5A gene. A rare variant SCN5A:p.Ala572Asp and the well-known functional SCN5A:p.His558Arg polymorphism. Both variants are shared between the mother and her daughter with a history of resuscitated SCD and syncopes, respectively. The second daughter with prodromal MVP as well as her healthy father and sister carried only the SCN5A:p.His558Arg polymorphism. Our study is highly suggestive of the contribution of SCN5A mutations as the potential genetic cause of the electric instability leading to ventricular arrhythmias in familial MVP cases with syncope and/or SCD history.

Mots clés: familial mitral valve prolapse; genetic arrhythmia substrate; SCN5A mutation; H558R polymorphism; syncope; resuscitated sudden cardiac death

Domaines: Génétique; Cardiologie et système cardiovasculaire

Hager Jaouadi, Alexis Théron, Jérôme Hourdain, Hélène Martel, Karine Nguyen, et al.. SCN5A Variants as Genetic Arrhythmias Triggers for Familial Bileaflet Mitral Valve Prolapse. International Journal of Molecular Sciences, 2022, 23 (22), pp.14447. ⟨10.3390/ijms232214447⟩. ⟨hal-03972542⟩