Mutant beta-myosin from patients with hypertrophic cardiomyopathy translocated actin filaments slower (0.09 and 0.17 µm/s for 403Arg->Gln and 908Leu->Val mutations) than normal controls (0.49 µm/s).
Hypertrophic cardiomyopathy is an important inherited disease. The phenotype has been linked, in some kindreds, to the beta-myosin heavy chain (beta-MHC) gene. Missense and silent mutations in the beta-MHC gene were used as markers to demonstrate the expression of mutant and normal cardiac beta-MHC gene message in skeletal muscle of hypertrophic cardiomyopathy patients. Mutant beta-myosin, also shown to be present in skeletal muscle by Western blot analysis, translocated actin filaments slower than normal controls in an in vitro motility assay. Thus, single amino acid changes in beta-myosin result in abnormal actomyosin interactions, confirming the primary role of missense mutations in beta-MHC gene in the etiology of hypertrophic cardiomyopathy.
Cuda et al. (Tue,) conducted a other in Hypertrophic cardiomyopathy (n=14). Mutant beta-myosin (403Arg->Gln or 908Leu->Val) vs. Normal beta-myosin was evaluated on Actin filament sliding velocity (µm/s). Mutant beta-myosin from patients with hypertrophic cardiomyopathy translocated actin filaments slower (0.09 and 0.17 µm/s for 403Arg->Gln and 908Leu->Val mutations) than normal controls (0.49 µm/s).