New Concepts in Hypertrophic Cardiomyopathies, Part I

Etiology of Familial Hypertrophic CardiomyopathyFamilial hypertrophic cardiomyopathy (FHCM) is a disease in which the dominant and characteristic phenotype is hypertrophy without obvious cause.In adults, the cause of this disease is always genetic; however, the proportion of individuals inheriting the disease as opposed to developing a de novo mutation (sporadic) remains to be determined.Because most sporadic cases transmit the gene to 50% of their offspring and become part of the familial pool, the need for genetic analysis is similar. 1 FHCM is a single-gene disorder inherited in an autosomal-dominant pattern for which 10 genes have been identified. 1 Each of the genes encodes for a sarcomeric protein, as shown in Table 1, with mutations in the ␤MHC (␤-myosin heavy chain) gene, 2,3 with MYBP-C (myosin-binding protein C) and troponin T probably accounting for 70% to 80% of all cases of FHCM.2,3 The total number of mutations is well over 100, and new mutations continue to be identified.4 The majority of the mutations are single-point missense mutations, meaning a single nucleotide has been substituted, which gives rise to a change in only 1 amino acid of the protein.The remainder of the mutations are small deletions or insertions, with 1 exception being a major deletion of Ͼ2000 bases.