Atrial fibrillation (AF) is the most common clinical arrhythmia and a major source of morbidity and mortality.¹ The underlying mechanisms for AF are highly heterogeneous and often related to associated structural heart disease.² However, in several large studies 10–30% of subjects have no obvious heart disease, and are labelled as primary or lone AF.¹

The identification of extended families with lone AF, and the mapping of discrete genetic loci in such families, raises the possibility that the heritable predisposition to this form of the arrhythmia is accessible.^3,4 Recently, the first gene for an inherited form of AF was identified in a family with autosomal dominant transmission.⁵ A mutation was found in the first transmembrane spanning domain of the potassium channel gene, KCNQ1, resulting in serine-glycine substitution (S140G). Mutations in other residues throughout this gene cause long QT syndrome type 1 (LQT1). Co-expression of the S140G mutant allele with KCNE1 in cells results in a gain of function with increased current density, and an alteration of channel activation and inactivation. These observations contrast with the reduction in current density seen with LQT1 associated mutations. The unique phenotype associated with this activating mutation includes persistent AF and, surprisingly, QT prolongation. This …