Abstract 17669: Compound heterozygosity of Cardiac Myosin Biding Protein C Gene Mutation Worsens Clinical Outcome of Hypertrophic Cardiomyopathy: Evidence from Comparison with Simple Founder Mutation Carriers
Background: Although founder mutations that arose from a common ancestor in hypertrophic cardiomyopathy are associated with a low mortality rate and mild clinical phenotypes, small fractions of founder mutations carriers exhibit unfavorable clinical courses. However, few data exist regarding the defining factors that modify phenotypes of founder mutations carriers.
Methods and Results: We screened sarcomere gene mutations in 450 probands with hypertrophic cardiomyopathy, and identified a prevalent founder mutation Val762Asp of the cardiac myosin-binding protein C gene in 33 subjects from 18 hypertrophic cardiomyopathy families. And we assessed genotype-phenotype correlations and investigated factors that contribute to phenotypic diversities of the mutation carriers. The simple cardiac myosin-binding protein C gene Val762Asp mutation was associated with a late onset (figure) and mild ventricular hypertrophy. Among those 33 carriers, 5 had additional sarcomere-genes mutations (3 in the cardiac myosin-binding protein C gene, 2 in the cardiac troponin T gene) and showed unfavorable phenotypes such as early disease onset and massive fibrosis of left ventricle determined by cardiac magnetic resonance images with late gadolinium enhancement.
Conclusion: These findings demonstrate that the cardiac myosin-binding protein C gene Val762Asp can develop severe phenotypes of hypertrophic cardiomyopathy when it was combined with another sarcomere gene mutation, although the simple mutation was associated with benign phenotypes. We suggest that these information may be useful in clinical practice and genetic counseling of carriers harboring the hypertrophic cardiomyopathy causing founder mutations.
- © 2012 by American Heart Association, Inc.