A MISSENSE MUTATION OF CARDIAC BETA-MYOSIN HEAVY-CHAIN GENE LINKED TO FAMILIAL HYPERTROPHIC CARDIOMYOPATHY IN AFFECTED JAPANESE FAMILIES

A novel missense mutation of the cardiac β-myosin heavy chain gene was detected in five unrelated Japanese patients and their affected family members with hypertrophic cardiomyopathy (HCM) by using the polymerase chain reaction (PCR)-DNA conformation polymorphism (DCP) analysis. Sequencing analysis revealed an A to G transion at codon 778 leading to replacement of the Asp residue, which is adjacent to the interaction sites of myosin heavy chain (MHC) with actin and is a conserved amino acid residue in various MHC across species, to the Gly residue. Linkage study of the mutation and two dinucleotides repeat markers of the cardiac β-MHC gene in three affected families showed that the mutation was on the same haplotype of the cardiac β-MHC gene and linked to HCM. These observations strongly suggest that the 778Asp to Gly mutations is the cause of HCM in these affected individuals. © 1993 Academic Press, Inc.