title: Spectrum of clinical phenotypes and gene variants in cardiac myosin-binding protein C mutation carriers with hypertrophic cardiomyopathy.
abstract: OBJECTIVE
  We studied the clinical and genetic features of hypertrophic cardiomyopathy (HCM) caused by mutations in the myosin-binding protein C gene (MYBPC3) in 110 consecutive, unrelated patients and family members of European descent.
  
  
  BACKGROUND
  Mutations in the MYBPC3 gene represent the cause of HCM in approximately 15% of familial cases. MYBPC3 mutations were reported to include mainly nonsense versus missense mutations and to be characterized by a delayed onset and benign clinical course of the disease in Japanese and French families. We investigated the features that characterize MYBPC3 variants in a large, unrelated cohort of consecutive patients.
  
  
  METHODS
  The MYBPC3 gene was screened by single-strand conformational polymorphism analysis and sequencing. The clinical phenotypes were analyzed using rest and 24-h electrocardiography, electrophysiology, two-dimensional and Doppler echocardiography and angiography.
  
  
  RESULTS
  We identified 13 mutations in the MYBPC3 gene: one nonsense, four missense and three splicing mutations and five small deletions and insertions. Of these, 11 were novel, and two were probably founder mutations. Patients with MYBPC3 mutations presented a broad range of phenotypes. In general, the 16 carriers of protein truncations had a tendency toward earlier disease manifestations (33 +/- 13 vs. 48 +/- 9 years; p = 0.06) and more frequently needed invasive procedures (septal ablation or cardioverter-defibrillator implantation) compared with the 9 carriers of missense mutations or in-frame deletions (12/16 vs. 1/9 patients; p < 0.01).
  
  
  CONCLUSIONS
  Multiple mutations, which include missense, nonsense and splicing mutations, as well as small deletions and insertions, occur in the MYBPC3 gene. Protein truncation mutations seem to cause a more severe disease phenotype than missense mutations or in-frame deletions.
authors.affiliation: Department of Internal Medicine, Charité, Humboldt University and Deutsches Herzzentrum, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Erdmann
authors.forename: J
authors.initials: J
authors.lastname: Raible
authors.forename: J
authors.initials: J
authors.lastname: Maki-Abadi
authors.forename: M
authors.initials: M
authors.lastname: Hummel
authors.forename: J
authors.initials: J
authors.lastname: Hammann
authors.forename: B
authors.initials: B
authors.lastname: Wollnik
authors.forename: E
authors.initials: E
authors.lastname: Frantz
authors.forename: E
authors.initials: E
authors.lastname: Fleck
authors.forename: R
authors.initials: R
authors.lastname: Hetzer
authors.forename: V
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D018703:Founder Effect; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C