Lifelong Left Ventricular Remodeling of Hypertrophic Cardiomyopathy Caused by a Founder Frameshift Deletion Mutation in the Cardiac Myosin-Binding Protein C Gene Among Japanese

ObjectivesWe studied the longitudinal evolution of hypertrophic cardiomyopathy (HCM) caused by a founder frameshift mutation in the cardiac myosin-binding protein C (MyBPC) gene.BackgroundMutations in the MyBPC gene have been associated with delayed expression of HCM and a good prognosis. Few studies, however, demonstrated the phenotype-genotype correlations in the longitudinal study.MethodsWe studied long-term evolution of clinical features of 15 unrelated families who were found to have an identical frameshift mutation in the MyBPC gene: a one-base deletion of a thymidine at nucleotide 11645 (V592fs/8).ResultsThirty-nine individuals in 15 families were genotype-positive. Thirty of the 39 individuals with the mutation were phenotype-positive. The disease penetrance was 100% in subjects ≥50 years and 65% in those <50 years. “End-stage” HCM (ejection fraction