title: Insights into genotype-phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3.
abstract: BACKGROUND
  Mutations in the cardiac myosin-binding protein C (MYBPC3) gene are frequently found as a cause of hypertrophic cardiomyopathy (HCM). However, only a few studies have analysed genotype-phenotype correlations in small series of patients. The present study sought to determine the clinical characteristics, penetrance and prognosis of HCM with an identical mutation in MYBPC3.
  
  
  METHODS
  154 non-related patients with HCM (aged 55±16 years, 100 (64.9%) males) were studied. 18 (11.7%) were found to have an identical mutation in the MYBPC3 gene (IVS23+1G→A). Pedigree analysis, including both clinical evaluation and genotyping, was performed.
  
  
  RESULTS
  152 individuals (mean age 37±18 years, 53.3% males) from 18 families were evaluated. 65 carriers of the IVS23+1G→A mutation were identified, 61.5% of whom met HCM diagnostic criteria. Penetrance of the disease increased with age, with 50% affected at 46 years of age. Males tended to develop the disease earlier than females. 7 (15.6%) had systolic dysfunction. Compared with the rest of the HCM cohort, probands with the mutation had more hypertrophy and were younger at diagnosis. There was a trend towards a reduced survival free from sudden death (SD) (HR 1.71; 95% CI 0.98 to 2.98, p=0.059). There were 17 SD cases in 12 families with the mutation.
  
  
  CONCLUSIONS
  The MYBPC3 IVS23+1G→A mutation is associated with middle-age onset disease and poor outcome, with a significant proportion of patients developing systolic impairment and a high SD risk profile.
authors.affiliation: Department of Cardiology, University Hospital Virgen Arrixaca, Murcia, Spain.
authors.forename: M José
authors.initials: MJ
authors.lastname: Oliva-Sandoval
authors.forename: Francisco
authors.initials: F
authors.lastname: Ruiz-Espejo
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.forename: Manuel
authors.initials: M
authors.lastname: Hermida-Prieto
authors.forename: Maria
authors.initials: M
authors.lastname: Sabater
authors.forename: Esperanza
authors.initials: E
authors.lastname: García-Molina
authors.forename: Martín
authors.initials: M
authors.lastname: Ortiz
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Rodríguez-García
authors.forename: Lucia
authors.initials: L
authors.lastname: Núñez
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gimeno
authors.forename: Alfonso
authors.initials: A
authors.lastname: Castro-Beiras
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés
mesh_terms: D000328:Adult; D000368:Aged; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D013030:Spain; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D000099163:Myosin Binding Protein C