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 individ uals, including 6 with HCM, was subjected to genetic and clinical assessmen t, Five exons of the cTnT gene were sequenced in all family members, A hete rozygous or homozygous T-340-->A (phe(110)-Ile) mutation in exon 9 of the c TnT gene was detected in 11 subjects. Morphological and functional evaluati on of the left and right ventricles by echocardiography revealed that 4 of 9 individuals heterozygous for the mutant allele exhibited HCM with moderat e cardiac hypertrophy, Cardiac hypertrophy and other clinical features in t he 2 subjects homozygous for the mutation were more severe than were those in heterozygous individuals with HCM, Thus, the clinical features of HCM du e 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.