Alterations of sarcomeric stoichiometry by nonsense mediated decay of MYBPC3-mRNA in hypertrophic cardiomyopathy patients with truncation mutations

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease with up to 40% of mutation-positive cases associated with heterozygous mutations in myosin binding protein C (cMyBP-C, MYBPC3). Most mutations in MYBPC3 lead to premature termination codons. This presumably induces nonsense mediated decay (NMD) of mutated MYBPC3-mRNA, resulting in reduction of functional cMyBP-C. This so-called haploinsufficiency disrupts the physiological stoichiometry of sarcomeric proteins and most likely contributes to disease development.