Genes, Geography and Geometry The "Critical Mass" in Hypertrophic Cardiomyopathy

HCM is caused by mutations in one of a number of genes. Approximately 450 different mutations have been discovered in genes for functional/structural proteins in the sarcomere (13 related genes) and myofilaments. Most of the alterations are missense, with a single amino acid residue substituted for another. The majority of HCM molecular defects lie in genes encoding functional and regulatory sarcomeric proteins such as beta-myosin heavy chain , actin, cardiac troponin T and I, and tropomyosin, as well as structural proteins, ie, myosin binding protein C (MYBPC) and titin.2 Identifying the specific gene mutation underlying the disease in individuals has more than an etiological relevance, as specific gene mutations may contribute to the different phenotypic and functional outcomes in patients suffering from HCM.