First description of germline mosaicism in familial hypertrophic cardiomyopathy

Familial hypertrophic cardiomyopathy is a genetically and phenotypically he terogeneous disease caused by mutations in seven sarcomeric protein genes. If is known to be transmitted as an. autosomal dominant trait with rare ale novo mutations. A French family in which two members are affected by hypertrophic cardiomyo pathy was clinically screened with electrocardiography and echocaradiograph y. Genetic analyses were performed on leucocyte DNA by haplotype analysis w ith microsatellite markers rs at the MYH7 locus and mutation screening by s ingle strand conformation polymorphism analysis. Two subjects exhibited sev ere hypertrophic cardiomyopathy. A mutation in the MYH7 gene was found in e xon 14 (Arg453Cys). The two affected patients were carriers of the mutation , which was not found in the circulating lymphocytes of their parents. Hapl otype analysis at the MYH7 locus with two intragenic microsatellite markers (MYOI and MYOII) and the absence of the mutation in the father's sperm DNA suggested that the mutation had been inherited from the mother. However ve r, it was neat found in either her fibroblasts or hair. This is the first description of germline mosaicism shown by molecular gene tic analysis in an autosomal dominant disorder and more especially in hyper trophic cardiomyopathy. This mosaicism had been inherited from the mother b ut did not affect her somatic cells. Such a phenomenon might account for so me de novo mutations in familial hypertrophic cardiomyopathy.