MOLECULAR-GENETIC BASIS OF HYPERTROPHIC CARDIOMYOPATHY - GENETIC-MARKERS FOR SUDDEN CARDIAC DEATH

Genetics of SCD in HCM, Hypertrophic cardiomyopathy (HCM) is an autoso mal dominant disease caused by mutations in sarcomeric proteins, The d isease is characterized by left ventricular hypertrophy in the absence of an increased external load, and myofibrillar disarray, A large num ber of mutations in genes coding for the beta-myosin heavy chain (beta -MyHC), cardiac troponin T (cTnT), cardiac troponin I, alpha-tropomyos in, myosin binding protein C (MyBP-C), and myosin light chain 1 and 2 in patients with HCM have been identified, Genotype-phenotype correlat ion studies have shown that mutations carry prognostic significance, T he Gly(256)GlU, Val(606)Met, and Leu(908)Val mutations in the beta-MyH C are associated with a benign prognosis, In contrast, Arg(403)Gln, Ar g(719)Trp, and Arg(453)Cys mutations are associated with a high incide nce of sudden cardiac death (SCD), Mutations in cTnT are associated wi th a mild degree of hypertrophy, but a high incidence of SCD, Mutation s in MyBP-C are associated with mild hypertrophy and a benign prognosi s, However, it has become evident that factors other than the underlyi ng mutations, such as genetic background and possibly environmental fa ctors, also modulate phenotypic expression of HCM.