title: Homozygotes for a R869G mutation in the beta -myosin heavy chain gene have a severe form of familial hypertrophic cardiomyopathy.
abstract: Familial Hypertrophic Cardiomyopathy (FHC) is an autosomal dominant disease characterised by ventricular hypertrophy, with predominant involvement of the interventricular septum. It is a monogenic disease with a high level of genetic heterogeneity (nine genes and more than 110 mutations reported so far). We describe a family with a new R869G mutation in the beta -myosin heavy chain gene (MYH7). This mutation was found in the heterozygous status in both parents and in the homozygous status in the two children. A haplotype analysis on the MYH7 locus with microsatellite markers showed that the same haplotype is transmitted within the family, suggesting a founder effect. Clinically, the father was asymptomatic with mild left ventricular hypertrophy on echocardiography. The mother had a mild form of hypertrophic cardiomyopathy and remained asymptomatic until 60 years old when an atrial fibrillation occurred. For the two children, clinical diagnosis was performed at 12 and 8 years and atrial fibrillation occurred at 17 years. For both children, the evolution was characterized by left ventricle (LV) systolic dysfunction and a severe dilatation of the left atrium before 40 years of age.
  
  
  CONCLUSIONS
  In this family, a new R869G mutation in the MYH7 gene was found. Interestingly, a mutation was found at the homozygous status for the first time in FHC. This finding suggests that this particular mutation is compatible with life, but for homozygous subjects, age at onset of symptoms was earlier and the disease much more severe than in the heterozygous subjects, suggesting a gene-dose effect.
authors.affiliation: Service de Biochimie B, Hôpital de la Salpêtrière, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: P
authors.initials: P
authors.lastname: Charron
authors.forename: C
authors.initials: C
authors.lastname: Leclercq
authors.forename: C
authors.initials: C
authors.lastname: Ledeuil
authors.forename: L
authors.initials: L
authors.lastname: Carrier
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: M
authors.initials: M
authors.lastname: Desnos
authors.forename: J B
authors.initials: JB
authors.lastname: Bouhour
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: J C
authors.initials: JC
authors.lastname: Daubert
authors.forename: M
authors.initials: M
authors.lastname: Komajda
authors.forename: B
authors.initials: B
authors.lastname: Hainque
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D005819:Genetic Markers; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D005819:Genetic Markers; D018995:Myosin Heavy Chains