title: Genotype-phenotype correlations in familial hypertrophic cardiomyopathy. A comparison between mutations in the cardiac protein-C and the beta-myosin heavy chain genes.
abstract: BACKGROUND
  The gene involved in familial hypertrophic cardiomyopathy on chromosome 11 was recently identified as the cardiac myosin binding protein-C (MyBP-C) gene. The phenotype of two families associated with mutation in this gene is described here and compared to that of five families with mutations in the beta-myosin heavy chain gene.
  
  
  RESULTS
  In adults (n = 33) bearing a splice acceptor site mutation in the MyBP-C gene, penetrance of familial hypertrophic cardiomyopathy was incomplete (69%) and ventricular hypertrophy mild. Among 37 clinical, electrocardiographic and echocardiographic parameters analysed, the only difference with the beta-MHC group (n = 35) was a shorter acceleration time of systolic flow in the pulmonary artery (P < 0.05). Sensitivity and specificity of diagnostic criteria were similar for the two genes. Cumulative survival rate for the splice acceptor site mutation (90% at 50 years old) was mid-way between that observed with a malignant (Arg403Leu: 42%) and a benign mutation (Arg403Trp: 100%) in the beta myosin heavy chain gene (P = 0.002).
  
  
  CONCLUSIONS
  The detailed phenotype associated with a mutation in the MyBP-C gene was no different from that associated with mutations in the beta myosin heavy chain gene, except for prognosis which appeared more benign. These preliminary results suggest that there is no locus-specific genotype-phenotype correlation for the two genes analysed.
authors.affiliation: Service de Cardiologie, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Charron
authors.forename: O
authors.initials: O
authors.lastname: Dubourg
authors.forename: M
authors.initials: M
authors.lastname: Desnos
authors.forename: R
authors.initials: R
authors.lastname: Isnard
authors.forename: A
authors.initials: A
authors.lastname: Hagege
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: L
authors.initials: L
authors.lastname: Carrier
authors.forename: F
authors.initials: F
authors.lastname: Tesson
authors.forename: J B
authors.initials: JB
authors.lastname: Bouhour
authors.forename: J C
authors.initials: JC
authors.lastname: Buzzi
authors.forename: J
authors.initials: J
authors.lastname: Feingold
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: M
authors.initials: M
authors.lastname: Komajda
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D009154:Mutation; D009218:Myosins / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D016019:Survival Analysis
chemical_list: D002097:C-Reactive Protein; D009218:Myosins