Review Molecular Genetics of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) is an autosomal dominant heart disease that is characterized by hypertrophy, often of the left ventricle, with predominant involvement of the interventricular septum in the absence of other causes of hipertrophy. The degree of hypertrophy, its distribution, patient age at onset, type and severity of clinical manifestations vary markedly. The natural course in certain families is ceased with sudden cardiac death, whereas in others sudden cardiac death is absent. The predominant cardiac pathology is myocyte hypertrophy and sarcomere disarray. The recent evolution of molecular genetics has facilitated the identification of the underlying genetic defects of HCM. Three genes and a fourth locus responsible for this disease have been identified, and structure-function analysis has shed significant light on the molecular basis of the disease. The ß myosin heavy chain gene is identified as the most responsible gene, and 36 mutations in this gene have been shown to be responsible for HCM. Mutations in the cardiac troponin T and a-tropomyosin genes have also been identified as related with inheritance of the disease. ldentification of the underlying genetic defects provides the opportunity to relate phenotype to specific genotypes. Thus, genetic identification of the mutation will identify the induviduals at risk of developing the disease before the presence of symptoms or the development of hypertrophy. If gene transfer therapy becomes available in the future, genotyping will certainly be a crucial examination in the patients with HCM.