Genetic heterogeneity of familial hypertrophic cardiomyopathy.

Familial hypertrophic cardiomyopathy (FHC) is characterized by an autosomal dominant transmission, a left ventricular hypertrophy and a myocardial disorganization. A first morbid gene coding for the beta-myosin heavy chain (beta-MHC) located on chromosome 14q11-q12 has been identified and genetic heterogeneity has been demonstrated. We performed linkage and haplotype analysis of 17 French families with microsatellite markers located to the beta-MHC locus and we searched for a new locus in a family for which the beta-MHC locus was excluded. Two novel missense mutations were identified in exon 13 of the beta-MHC resulting in the replacement of 403 arginine by a leucine or a tryptophan in two different families. In one other family, systematic screening of the genome with highly informative markers allowed us to find a new locus for FHC on chromosome 11.