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

Background Familial hypertrophic cardiomyopathyis a phenotypically and genetically heterogeneous disease. In some families, the disease is linked to the CMH2 locus on chromosome 1q3, in which the cardiac troponin Tgene ( TNNT2) has been identified as the disease gene. The mutations found in this gene appear to be associated with incomplete penetrance and poor prognosis. Because mutational hot spots offer unique possibilities for analysis of genotype-phenotype correlations, new missense mutationsthat could define such hot spots in TNNT2were looked for in unrelated French families with familial hypertrophic cardiomyopathy. Methods and Results Family members were genotyped with microsatellite markers to detect linkage to the four known disease loci. In family 715, analyses showed linkage to CMH2 only. To accurately position potential mutations on TNNT2, its partial genomic organizationwas established. Screening for mutations was performed by single-strand conformation polymorphismanalysis and sequencing...