title: Phenotypic variation of familial hypertrophic cardiomyopathy caused by the Phe(110)-->Ile mutation in cardiac troponin T.
abstract: Mutation of the cardiac troponin T (cTnT) gene is a genetic determinant of familial 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.
authors.affiliation: Department of Clinical Laboratory Medicine, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Ichihara
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: T
authors.initials: T
authors.lastname: Nagasaka
authors.forename: H
authors.initials: H
authors.lastname: Ishihara
authors.forename: N
authors.initials: N
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Yokota
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004247:DNA / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020107:Troponin T / Q000235:genetics* / Q000378:metabolism
chemical_list: D020107:Troponin T; D004247:DNA