Mechanisms of dysfunction in patient-derived cardiomyocytes with the hypertrophic cardiomyopathy-myosin binding protein-C e258K mutation

Abstract

Mutations in cardiac myosin binding protein-C (cMyBP-C) are the most common cause of hypertrophic cardiomyopathy (HCM). We recently described the highly penetrant MYBPC3-c.772G>A (p.E258K) mutation with founder effect in Tuscany, Italy. Isolated myofibrils from patient myectomies indicated accelerated cross-bridge kinetics and higher energy cost of tension. Concurrently, prolonged action potentials and calcium transient duration preserves twitch contraction amplitude and duration in intact cells and trabeculae (Pioner et al., Biophys J, 2020;118:35a).