Familial Hypertrophic Cardiomyopathy: From Mutations to Functional Defects

摘要: Hypertrophic cardiomyopathy is characterized by left and/or right ventricular hypertrophy, which usually asymmetric and involves the interventricular septum. Typical morphological changes include myocyte hypertrophy disarray surrounding areas of increased loose connective tissue. Arrhythmias premature sudden deaths are common. familial in majority cases transmitted as an autosomal-dominant trait. The results molecular genetics studies have shown that hypertrophic a disease sarcomere involving mutations 7 different genes encoding proteins myofibrillar apparatus: ss-myosin heavy chain, myosin essential light regulatory cardiac troponin T, I, alpha-tropomyosin, binding protein C. In addition to this locus heterogeneity, there wide allelic since numerous been found all these genes. recent development animal models vitro analyses allowed better understanding pathophysiological mechanisms associated with cardiomyopathy. One can thus tentatively draw following cascade events: mutation leads poison polypeptide would be incorporated into sarcomere. This alter sarcomeric function result (1) altered then (2) alteration structure. Some induce functional impairment support pathogenesis hypothesis "hypocontractile" state followed compensatory hypertrophy. Other hyperfunction determine "hypercontractile" directly other mechanistic linking genetic defects now key issues how alterations basic contractile unit cardiomyocyte phenotype heart.