Altered protein quality control in heart tissue of patients with hypertrophic cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease with a prevalence of 1:200 and is caused by mutations in genes encoding sarcomere proteins. Age of onset and disease-severity vary greatly between patients. The mechanisms that underlie this variation are unknown. Recent findings suggest an important role for secondary disease-modifiers to underlie HCM susceptibility. Because keeping mutant protein levels at a low level is an important function of the protein quality control (PQC) system, we hypothesize that impairment of the PQC system may contribute to HCM development.