Phenotype and prognostic correlations of the converter region mutations affecting the β myosin heavy chain

Heart. 2015 Jul;101(13):1047-53. doi: 10.1136/heartjnl-2014-307205. Epub 2015 May 2.

Abstract

Objectives: The prognostic value of genetic studies in cardiomyopathies is still controversial. Our objective was to evaluate the outcome of patients with cardiomyopathy with mutations in the converter domain of β myosin heavy chain (MYH7).

Methods: Clinical characteristics and survival of 117 affected members with mutations in the converter domain of MYH7 were compared with 409 patients described in the literature with mutations in the same region.

Results: Twenty-five mutations were evaluated (9 in our families including 3 novel (Ile730Asn, Asp717Gly and Arg719Pro)). Clinical diagnoses were hypertrophic (n=407), dilated (n=15), non-compaction (n=4) and restrictive (n=5) cardiomyopathies, unspecified cardiomyopathy (n=11), sudden death (n=50) and 35 healthy carriers. One hundred eighty-four had events (cardiovascular death or transplant). Median event-free survival was 50±2 years in our patients and 53±3 years in the literature (p=0.27). There were significant differences in the outcome between mutation: Ile736Thr had fewer events than other mutations in the region (p=0.01), while Arg719Gln (p<0.01) had reduced event-free survival.

Conclusions: Mutations in the converter region are generally associated with adverse prognosis although there are differences between mutations. The identification of a mutation in this particular region provides important prognostic information that should be considered in the clinical management of affected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiac Myosins / genetics*
  • Cardiomyopathies* / classification
  • Cardiomyopathies* / diagnosis
  • Cardiomyopathies* / genetics
  • Echocardiography / methods
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Myosin Heavy Chains / genetics*
  • Pedigree
  • Phenotype
  • Prognosis
  • Spain
  • Survival Analysis

Substances

  • MYH7 protein, human
  • Cardiac Myosins
  • Myosin Heavy Chains