NOVEL MISSENSE MUTATION IN CARDIAC TROPONIN-T GENE FOUND IN JAPANESE PATIENT WITH HYPERTROPHIC CARDIOMYOPATHY

Familial hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy with an autosomal dominant pattern of inheritance. The disease bearin g genes for HCM in HCM families have been identified as beta-myosin he avy chain, alpha-tropomyosin, cardiac troponin T (cTnT) and myosin bin ding protein-C genes. In the present study, we searched for the mutati ons in the cTnT gene in Japanese HCM patients. Single-strand conformat ion polymorphism gel analysis of polymerase chain reaction-amplified p roduct was used to search for the mutations in the exons 8, 9 and 15 o f the cTnT gene from 60 familial HCM patients, Clinical studies of the family members were performed and the incidence of sudden or disease- related deaths within the family was also examined. We have identified a novel missense mutation in exon 9 (Ala104Val) of the cTnT gene in a patient with familial HCM. Because the missense mutation was found at the residue conserved through chicken to humans and was not detected in the more than 50 normal controls, it was suggested that this missen se mutation is the cause of HCM in this family. Although the affected family members presented moderate hypertrophy of the left ventricular wall, they were symptomatic and there was a high incidence of sudden d eath in her family members. Among Japanese patients with familial HCM, a novel missense mutation (Ala104Val) in the cTnT gene was identified . Familial HCM is genetically heterogeneous in Japanese HCM patients a s observed in Caucasian kindreds. The disease in the kindred was sever e and there was a high incidence of sudden or disease-related deaths i n the kindred with this mutation. (C) 1997 Academic Press Limited.