A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation.

A point mutation in exon 13 of the beta cardiac myosin heavy chain (MHC) gene is present in all individuals affected with familial hypertrophic cardiomyopathy (FHC) from a large kindred. This missense mutation converts a highly conserved arginine residue (Arg-403) to a glutamine. Affected individuals from an unrelated family lack this missense mutation, but instead have an alpha/beta cardiac MHC hybrid gene. Identification of two unique mutations within cardiac MHC genes in all individuals with FHC from two unrelated families demonstrates that defects in the cardiac MHC genes can cause this disease. The pathology resulting from a missense mutation at residue 403 further suggests that a critical function of myosin is disrupted by this mutation.