title: Clinical features and prognostic implications of familial hypertrophic cardiomyopathy related to the cardiac myosin-binding protein C gene.
abstract: BACKGROUND
  Little information is available on phenotype-genotype correlations in familial hypertrophic cardiomyopathy that are related to the cardiac myosin binding protein C (MYBPC3) gene. The aim of this study was to perform this type of analysis.
  
  
  RESULTS
  We studied 76 genetically affected subjects from nine families with seven recently identified mutations (SASint20, SDSint7, SDSint23, branch point int23, Glu542Gln, a deletion in exon 25, and a duplication/deletion in exon 33) in the MYBPC3 gene. Detailed clinical, ECG, and echocardiographic parameters were analyzed. An intergene analysis was performed by comparing the MYBPC3 group to seven mutations in the beta-myosin heavy-chain gene (beta-MHC) group (n=52). There was no significant phenotypic difference among the different mutations in the MYBPC3 gene. However, in the MYBPC3 group compared with the beta-MHC group, (1) prognosis was significantly better (P<0.0001), and no deaths occurred before the age of 40 years; (2) the age at onset of symptoms was delayed (41+/-19 versus 35+/-17 years, P<0.002); and (3) before 30 years of age, the phenotype was particularly mild because penetrance was low (41% versus 62%), maximal wall thicknesses lower (12+/-4 versus 16+/-7 mm, P<0.03), and abnormal T waves less frequent (9% versus 45%, P<0.02).
  
  
  CONCLUSIONS
  These results are consistent with specific clinical features related to the MYBPC3 gene: onset of the disease appears delayed and the prognosis is better than that associated with the beta-MHC gene. These findings could be particularly important for the purpose of clinical management and genetic counseling in familial hypertrophic cardiomyopathy.
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: M
authors.initials: M
authors.lastname: Bennaceur
authors.forename: L
authors.initials: L
authors.lastname: Carrier
authors.forename: A C
authors.initials: AC
authors.lastname: Camproux
authors.forename: R
authors.initials: R
authors.lastname: Isnard
authors.forename: A
authors.initials: A
authors.lastname: Hagege
authors.forename: J M
authors.initials: JM
authors.lastname: Langlard
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: P
authors.initials: P
authors.lastname: Richard
authors.forename: B
authors.initials: B
authors.lastname: Hainque
authors.forename: J B
authors.initials: JB
authors.lastname: Bouhour
authors.forename: K
authors.initials: K
authors.lastname: Schwartz
authors.forename: M
authors.initials: M
authors.lastname: Komajda
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics; D011379:Prognosis; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D018995:Myosin Heavy Chains; D000099163:Myosin Binding Protein C