Novel missense mutation in alpha-tropomyosin gene found in Japanese patients with hypertrophic cardiomyopathy

Abstract

We have searched for mutations in alpha-tropomyosin gene in 50 Japanese patients with hypertrophic cardiomyopathy (HCM) by means of polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. Two missense mutations of the alpha-tropomyosin gene were detected in Japanese patients with familial HCM. Sequencing analysis revealed a C to T transition at codon 63 leading to a replacement of Ala with Val residue, and a G to A transition with replacement of Asp by Asn at codon 175. These missense mutations were found at residues which were markedly conserved across the species, and have been reported to interact with troponin T. This is the first report on a mutant alpha-tropomyosin gene in a Japanese population. Familial HCM is a genetically heterogeneous disease in Japanese patients, similar to that reported in Caucasian kindreds.