title: Codon 102 of the cardiac troponin T gene is a putative hot spot for mutations in familial hypertrophic cardiomyopathy.
abstract: BACKGROUND
  Familial hypertrophic cardiomyopathy is a phenotypically and genetically heterogeneous disease. In some families, the disease is linked to the CMH2 locus on chromosome 1q3, in which the cardiac troponin T gene (TNNT2) has been identified as the disease gene. The mutations found in this gene appear to be associated with incomplete penetrance and poor prognosis. Because mutational hot spots offer unique possibilities for analysis of genotype-phenotype correlations, new missense mutations that could define such hot spots in TNNT2 were looked for in unrelated French families with familial hypertrophic cardiomyopathy.
  
  
  RESULTS
  Family members were genotyped with microsatellite markers to detect linkage to the four known disease loci. In family 715, analyses showed linkage to CMH2 only. To accurately position potential mutations on TNNT2, its partial genomic organization was established. Screening for mutations was performed by single-strand conformation polymorphism analysis and sequencing. A new missense mutation, Arg102Leu, was identified in affected members of family 715 because of a G-->T transversion located in the 10th exon of the gene. Penetrance of this new mutation is complete; echocardiographic data show a wide range of hypertrophy; and there was no sudden cardiac death in this family.
  
  
  CONCLUSIONS
  The codon 102 of the TNNT2 gene is a putative mutational hot spot in familial hypertrophic cardiomyopathy and is associated with phenotypic variability. Analysis of more pedigrees carrying mutations in this codon is necessary to better characterize the clinical and prognostic implications of TNNT2 mutations.
authors.affiliation: Unité de Recherches 153 de l'INSERM, Paris, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Forissier
authors.forename: L
authors.initials: L
authors.lastname: Carrier
authors.forename: H
authors.initials: H
authors.lastname: Farza
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: J
authors.initials: J
authors.lastname: Bercovici
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: B
authors.initials: B
authors.lastname: Hainque
authors.forename: P J
authors.initials: PJ
authors.lastname: Townsend
authors.forename: M H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: S
authors.initials: S
authors.lastname: Fauré
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: A
authors.initials: A
authors.lastname: Millaire
authors.forename: A A
authors.initials: AA
authors.lastname: Hagège
authors.forename: M
authors.initials: M
authors.lastname: Desnos
authors.forename: M
authors.initials: M
authors.lastname: Komajda
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D003062:Codon; D004452:Echocardiography; D004562:Electrocardiography; D005091:Exons; D005190:Family; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014336:Troponin / Q000235:genetics*; D020107:Troponin T
chemical_list: D003062:Codon; D014336:Troponin; D020107:Troponin T