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Insights into genotype–phenotype correlation in hypertrophic cardiomyopathy. Findings from 18 Spanish families with a single mutation in MYBPC3
  1. M José Oliva-Sandoval1,
  2. Francisco Ruiz-Espejo2,
  3. Lorenzo Monserrat3,
  4. Manuel Hermida-Prieto3,
  5. Maria Sabater2,
  6. Esperanza García-Molina2,
  7. Martín Ortiz3,
  8. M Isabel Rodríguez-García3,
  9. Lucia Núñez3,
  10. Juan R Gimeno1,
  11. Alfonso Castro-Beiras3,
  12. Mariano Valdés1
  1. 1Department of Cardiology, University Hospital Virgen de la Arrixaca, Murcia, Spain
  2. 2Department of Clinical Analysis, Molecular Biology Unit, University Hospital Virgen Arrixaca, Murcia Spain
  3. 3Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain
  1. Correspondence to Dr Juan R Gimeno, Department of Cardiology, University Hospital Virgen Arrixaca, Ctra Murcia-Cartagena s/n., El Palmar (30120), Murcia, Spain; jgimeno{at}


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.

  • Hypertrophic cardiomyopathy
  • genetics
  • genotype–phenotype correlation
  • MYBPC3

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  • Funding This study has been partly funded by national grants from the FIS (PI050377, PI070926) and by the Cardiovascular Research Network (RECAVA) from the Health Institute Carlos III (C03/01, RD06/0014/0017, RD06/0014/0018).

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Ethics Committee of University Hospital Virgen Arrixaca, Murcia.

  • Provenance and peer review Not commissioned; externally peer reviewed.