Cytosine methylation confers instability on the cardiac troponin T gene in hypertrophic cardiomyopathy

Subjects with HCM caused by mutations in the cardiac troponin T (cTNT) gene have been clinically shown to be at increased risk of sudden death, 6 which may occur even in the absence of marked morphological abnormalities. 7 Since incomplete penetrance of the clinical phenotype, measured by ECG and echocardiographic parameters, is one of the hallmarks of "troponin" disease, the identification ofcTNT mutation in probands would facilitate identification of "at risk" relatives who may not fulfil clinical diagnostic criteria. T mismatches, resulting from deamination of 5mC, involve different, less efficient mechanisms of repair. 18 It is estimated that 30-40% of point mutations which occur within the genome are a result of C->T transitions (or a corresponding G->A transition in the opposite strand) within CpG dinucleotides. Since cytosine methylation could account for the high rate of such transition mutations observed in cTNT, we investigated the methylation profile of exons 8 and 9 of this gene with the aim of determining regions of genetic instability.