SKELETAL-MUSCLE EXPRESSION AND ABNORMAL FUNCTION OF BETA-MYOSIN IN HYPERTROPHIC CARDIOMYOPATHY

Hypertrophic cardiomyopathy is an important inherited disease. The phe notype has been linked, in some kindreds, to the beta-myosin heavy cha in (beta-MHC) gene. Missense and silent mutations in the beta-MHC gene were used as markers to demonstrate the expression of mutant and norm al cardiac beta-MHC gene message in skeletal muscle of hypertrophic ca rdiomyopathy patients. Mutant beta-myosin, also shown to be present in skeletal muscle by Western blot analysis, translocated actin filament s slower than normal controls in an in vitro motility assay. Thus, sin gle amino acid changes in beta-myosin result in abnormal actomyosin in teractions, confirming the primary role of missense mutations in beta- MHC gene in the etiology of hypertrophic cardiomyopathy.