Phenotypic variation of familial hypertrophic:: cardiomyopathy caused by the Phe110→IIe mutation in cardiac troponin T

Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of familiar hypertrophic cardiomyopathy (HCM). A Japanese family of 14 individuals, including 6 with HCM, was subjected to genetic and clinical assessment, Five exons of the cTnT gene were sequenced in all family members, A heterozygous or homozygous T-340-->A (phe(110)-Ile) mutation in exon 9 of the cTnT gene was detected in 11 subjects. Morphological and functional evaluation of the left and right ventricles by echocardiography revealed that 4 of 9 individuals heterozygous for the mutant allele exhibited HCM with moderate cardiac hypertrophy, Cardiac hypertrophy and other clinical features in the 2 subjects homozygous for the mutation were more severe than were those in heterozygous individuals with HCM, Thus, the clinical features of HCM due to the Phe(110)-Ile mutation in the cTnT gene appear to be modified by a gene dosage effect, Copyright (C) 2000 S. Karger AG, Basel.