A homozygous MYBPC3 gene mutation associated with a severe phenotype and a high risk of sudden death in a family with hypertrophic cardiomyopathy.

Genetic studies can play a key role in the comprehensive evaluation of familiar hypertrophic cardiomyopathy and in the development of individualized medicine. Although only a few cases have been described, there exists a group of patients with complex genotypes that are associated with severe disease manifestations and a high risk of sudden death. We describe a family in which some members experienced the early development of systolic and diastolic dysfunction while others experienced sudden death at a young age. We identified a novel homozygous mutation (IVS6+5G>A) in the myosin-binding protein-C gene that explained the phenotype of affected individuals and that enabled us to estimate the risk in other family members and to offer genetic counseling.