Codon 102 of the Cardiac Troponin T Gene Is a Putative Hot Spot for Mutations in Familial Hypertrophic Cardiomyopathy

Abstract

The codon 102 of the TNNT2 gene is a putative mutational hot spot in familial hypertrophic cardiomyopathy and is associated with phenotypic variability. Analysis of more pedigrees carrying mutations in this codon is necessary to better characterize the clinical and prognostic implications of TNNT2 mutations.

Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy

“…All the known cTnT-related FHC alleles in humans map within 2 major functional domains (28,29). Our previously described cTnT-FHC transgenic mouse model demonstrated the pathophysiological effects of disrupting the COOH-terminal α-TM-TnI-TnC binding domain of cTnT (17).…”

Identification of a contractile deficit in adult cardiac myocytes expressing hypertrophic cardiomyopathy–associated mutant troponin T proteins

“…We focused on these 2 missense mutations because of their malignant clinical outcomes (15), their putative shared structural domain for tropomyosin interaction (7), and the finding that codon 92 is an apparent mutational hot spot (16). The hypothesis tested was that the I79N and R92Q mutants would be expressed and incorporated into the sarcomere and would directly alter calcium-activated force generation of the adult single cardiac myocyte.…”

Genetic Bases of Hypertrophic Cardiomyopathy

“…Missense mutation in a total of 10, localized in exons 8,9,11, 14, and 16 predominate 41,57 . De novo mutation in exon 9, Arg 92 Trp, has recently been reported 58 .…”

“…It has been possible by reanalysis of the genome organization of the gene of cardiac troponin T to identify codon 102 as the point susceptible to mutation 57 . Distinct characteristics were observed in one of the mutations involving this codon, Arg102Leu, in which high penetrance with a marked degree of hypertrophy was noted.…”