Pathogenesis of Inherited Forms of Dilated Cardiomyopathy

In 1990, Geisterfer-Lowrance et al. reported the first evidence of a gene defect underlying a form of intrinsic heart-muscle disease. They found that a mutation in the gene encoding the contractile protein β-myosin heavy chain results in familial hypertrophic cardiomyopathy.1 Since then, mutations in seven other genes, all encoding proteins of the myofibrillar apparatus, the fundamental contractile unit of the cardiomyocyte, have been found to cause familial hypertrophic cardiomyopathy.2,3 These proteins include sarcomeric proteins (ventricular myosin light chains 1 and 2, cardiac troponin I and T, α-tropomyosin, α-cardiac actin) and an intrasarcomeric cytoskeletal protein (myosin-binding protein C). Although the . . .