Mutations in the cardiac troponin T gene show various prognoses in Japanese patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder resulting from mutations in genes for at least 15 various sarcomere-related proteins including cardiac β-myosin heavy chain, cardiac myosin-binding protein C, and cardiac troponin T. The troponin T gene (TNNT2) mutation has the third incidence of familial HCM, and the genotype–phenotype correlation of this gene still remains insufficient in Japanese familial HCM. Therefore, in the present study, we focused on screening the TNNT2 mutation in 173 unrelated Japanese patients with familial HCM, and found three reported mutations and a new mutation of TNNT2 in 11 individuals from four families. In these families, two individuals from one family had double mutations, Arg130Cys and Phe110Ile, six individuals from two other families had an Arg92Trp mutation, and one individual of another family had a new mutation, Ile79Thr, of TNNT2. The phenotype of each family was often different from reported cases, even if they had the same genetic mutation. In addition, families with the same genetic mutation showed a similar trend in the phenotype, but it was not exactly the same. However, sudden death in youth was observed in all of these families. Although the type of genetic mutation is not useful for predicting prognosis in HCM, the possibility of sudden cardiac death remains. Therefore, the prognosis of individuals bearing the TNNT2 mutation with familial HCM should be more carefully observed from birth.