Hypertrophic cardiomyopathy (HCM) is an inherited disease characterized by extensive left ventricular hypertrophy with no preexistent hypertension or valve disease. Histological examination shows myocyte and myofibrillar disarray in the hypertrophied area. Genetic studies have demonstrated that HCM is linked, in some families, to chromosome 14, where the alpha and beta cardiac myosin heavy chain (MHC) genes are located. Recently, two types of mutations in the gene which encodes for the beta MHC isoform have been found: missense mutations in highly conserved residues of the MHC gene and an alpha/beta hybrid gene. Since the beta MHC gene also encodes the slow MHC isoform of skeletal muscle, we have purified myosin using soleus skeletal muscle biopsies from patients carrying two distinct point mutations, Arg403Gln and Leu908Val, and normal controls. We have found that, in the Arg403Gln mutation, the abnormal MHC isoform is expressed in skeletal muscle. Using the sliding actin in vitro motility assay, we also have demonstrated that myosin purified from both Arg403Gln and Leu908Val mutations behaves abnormally with respect to myosin purified from normal controls. These findings can be very useful in understanding the molecular pathogenesis of this disease.
