Molecular Epidemiology of Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a geneticallyheterogeneous autosomal dominant trait, in which affected individuals develop left ventricular hypertrophy orthickening of the heart wall (Fig. 1) (for reviews, seeFatkin et al. 2000; Towbin 2000; Seidman and Seidman2001). Although affected individuals may live for manyyears without obvious clinical signs of their disease,many of these individuals go on to develop chest pain,dyspnea, palpitations, and even sudden death. Associatedwith cardiac hypertrophy, heart muscle from affected individuals demonstrates myocyte disarray and fibrosis(Fig. 2). Eleven different disease genes have been identified, including β-cardiac myosin (MHC) (Geisterfer-Lowrance et al. 1990), cardiac actin (Olson et al. 2000),α-tropomyosin (Thierfelder et al. 1994), cardiac troponinT (TNT; Thierfelder et al. 1994), cardiac myosin-bindingprotein C (MyBP-C; Watkins et al. 1995), essentialmyosin light chain (MLC; Poetter et al. 1996), regulatorymyosin light chain (Poetter et al. 1996), cardiac troponinI (TNI; Kimura et al. 1997), α-cardiac myosin (Niimuraet al. 2002), and titin (Gerull et al. 2002). Each of thesedisease genes encodes a component of the cardiac sarcomere (Fig. 3). Multiple different mutations have beenidentified in each gene (Table 1). That is, HCM displaysboth intergenic and intragenic heterogeneity. The distribution of mutations (Table 1) found in HCM patients i...