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.
Dausse
E
E
INSERM U127, Hôpital Lariboisière, Paris, France.
Schwartz
K
K
D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002883:Chromosomes, Human, Pair 14; D005091:Exons; D005260:Female; D005602:France; D015321:Gene Rearrangement; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D009218:Myosins / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D011110:Polymorphism, Genetic
D005819:Genetic Markers; D009218:Myosins