Abstract Aims The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to
ventricular arrhythmias. Despite considerable efforts, its genetic basis and cellular
mechanisms remain largely unknown. The objective of this study was to identify a new
susceptibility gene for BrS through familial investigation. Methods and results Whole-exome
sequencing performed in a three-generation pedigree with five affected members allowed
the identification of one rare non-synonymous substitution (p. R211H) in RRAD, the gene …

Introduction The Brugada syndrome (BrS) is an inherited cardiac disorder predisposing to
ventricular arrhythmias and sudden death. In the present day, only 30% of BrS cases have
known genetic causes. Using whole-exome sequencing in a large pedigree with affected
members, we identified a rare variant (p. R211H) in RRAD, the gene encoding Rad GTPase.
Objective The aim of this work was to elucidate the mechanisms by which the RRAD p.
R211H variant leads to BrS. Methods The study was performed in two cell models, ie …