LQT8 mutations induce action potential prolongation and arrhythmia in induced pluripotent stem cell derived cardiomyocytes

Abstract

Long QT syndrome type 8 (LQT8) is a severe disorder caused by a point mutation in CaV1.2 L-type Ca2+ channels, resulting in a prolonged QT interval, arrhythmia and sudden cardiac death. The canonical and most common mutation, G406R, occurs most often within the mutually exclusive exon 8a, found in 20% of cardiac CaV1.2 variants. Yet, even heterozygous expression (10% of cardiac channels) of G406R is hugely deleterious. Despite this limited expression, the patients exhibit severe symptoms, which are often fatal in early childhood.