Identification of a New Gain-of-Function Mutation of NaV1.5 Associated with Atrial Fibrillation in an African-American Family

Abstract

Mutations and rare genetic variants in cardiac voltage-gated Nav1.5 channel, have been associated with inherited predisposition to ventricular arrhythmias such as in long QT syndrome and Brugada syndrome. More recently, Nav1.5 mutations have been identified in families segregating atrial fibrillation (AF), the most common arrhythmia in adults. Here, we evaluated the functional and biophysical properties of an Nav1.5 mutation associated with early-onset AF in an African-American family. The African-American proband presented with early-onset AF with controlled ventricular rates on no AV nodal blockers strongly implicating conduction disease.