CARDIAC MYOSIN BINDING PROTEIN-C GENE SPLICE ACCEPTOR SITE MUTATION IS ASSOCIATED WITH FAMILIAL HYPERTROPHIC CARDIOMYOPATHY

Familial hypertrophic cardiomyopathy (FHC) is an autosomal dominant disease characterized by a ventricular hypertrophy predominantly affecting the inter-ventricular septum and associated with a large extent of myocardial and myofibrillar disarray1. It is the most common cause of sudden death in the young. In the four disease loci found, three genes have been identified which code for β-myosin heavy chain, cardiac tro-ponin T and α-tropomyosin2–7. Recently the human cardiac myosin binding protein-C (MyBP-C) gene was mapped to chromosome 11p11.2 (ref. 8), making this gene a good candidate for the fourth locus, CMH4 (ref. 5). Indeed, MyBP-C is a substantial component of the myofibrils that interacts with several proteins of the thick filament of the sarcomere9–13. In two unrelated French families linked to CMH4, we found a mutation in a splice acceptor site of the MyBP-C gene, which causes the skipping of the associated exon and could produce truncated cardiac MyBP-Cs. Mutations in the cardiac MyBP-C gene likely cause chromosome 11-linked hypertrophic cardiomyopathy, further supporting the hypothesis that hypertrophic cardiomyopathy results from mutations in genes encoding contractile proteins. © 1995 Nature Publishing Group.