The purpose of this project is to determine the chromosomal location of the genes responsible for hypertrophic cardiomyopathy (HCM). This type of heart disease is diagnosed by echocardiography. Its clinical manifestations are highly variable including anatomical abnormalities only, cardiac failure, left ventricular outflow obstruction and/or sudden death. Linkage analysis has identified the myosin beta heavy chain locus as being the site of the mutation in about 50% of families. We have identified two distinct point mutations in this gene in separate families. In one family substitution of arginine for glutamine is at position 403 in the protein and in the other family there is substitution of valine for leucine at position 908. These mutations are thought to interfere with function of cardiac myosin and alter contractility. These results provide the opportunity for genotypic diagnosis in these families so that the full spectrum of disease manifestation can be defined.
