SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome

AbstractLong OT syndrome (LOT) is an inherited disorder that causes sudden death from cardiac arrhythmias, specifically torsade de pointes and ventricular fibrillation. We previously mapped three LQT loci: LQT1 on chromosome 11p15.5, LQT2 on 7835-36, and LQT3 on 3p21-24. Here we report genetic linkage between LQT3 and polymorphisms within SCN5A, the cardiac sodium channel gene. Single strand conformation polymorphism and DNA sequence analyses reveal identical intragenic deletions of SCN5A in affected members of two unrelated LOT families. The deleted sequences reside in a region that is important for channel inactivation. These data suggest that mutations in SCN5A cause chromosome 3-linked LOT and indicate a likely cellular mechanism for this disorder