title: First description of germline mosaicism in familial hypertrophic cardiomyopathy.
abstract: Familial hypertrophic cardiomyopathy is a genetically and phenotypically heterogeneous disease caused by mutations in seven sarcomeric protein genes. It is known to be transmitted as an autosomal dominant trait with rare de novo mutations.A French family in which two members are affected by hypertrophic cardiomyopathy was clinically screened with electrocardiography and echocardiography. Genetic analyses were performed on leucocyte DNA by haplotype analysis with microsatellite markers at the MYH7 locus and mutation screening by single strand conformation polymorphism analysis. Two subjects exhibited severe hypertrophic cardiomyopathy. A mutation in the MYH7 gene was found in exon 14 (Arg453Cys). The two affected patients were carriers of the mutation, which was not found in the circulating lymphocytes of their parents. Haplotype 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, it was not found in either her fibroblasts or hair. This is the first description of germline mosaicism shown by molecular genetic analysis in an autosomal dominant disorder and more especially in hypertrophic cardiomyopathy. This mosaicism had been inherited from the mother but did not affect her somatic cells. Such a phenomenon might account for some de novo mutations in familial hypertrophic cardiomyopathy.
authors.affiliation: Service de Cardiologie, Hôpital Trousseau, 37044 Tours Cedex, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Forissier
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: S
authors.initials: S
authors.lastname: Briault
authors.forename: C
authors.initials: C
authors.lastname: Ledeuil
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: B
authors.initials: B
authors.lastname: Charbonnier
authors.forename: L
authors.initials: L
authors.lastname: Carrier
authors.forename: C
authors.initials: C
authors.lastname: Moraine
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: M
authors.initials: M
authors.lastname: Komajda
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: B
authors.initials: B
authors.lastname: Hainque
mesh_terms: D000293:Adolescent; D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D009030:Mosaicism; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D018995:Myosin Heavy Chains