NOVEL MISSENSE MUTATION IN ALPHA-TROPOMYOSIN GENE FOUND IN JAPANESE PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

We have searched for mutations in alpha-tropomyosin gene in 50 Japanes e patients with hypertrophic cardiomyopathy (HCM) by means of polymera se chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis, Two missense mutations of the alpha-tropomyosin gene were d etected in Japanese patients with familial HCM. Sequencing analysis re vealed 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 whic h were markedly conserved across the species, and have been reported t o interact with troponin T. This is the first report on a mutant alpha -tropomyosin gene in a Japanese population. Familial HCM is a genetica lly heterogeneous disease in Japanese patients, similar to that report ed in Caucasian kindreds. (C) 1995 Academic Press Limited