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Prevalence of desmosomal protein gene mutations in patients with dilated cardiomyopathy

Perry Elliott1, Constantinos O'Mahony, Petros Syrris

  • 1Inherited Cardiac Diseases Unit, University College London/The Heart Hospital (UCL Hospitals NHS trust), London, UK. perry.elliott@ucl.ac.uk

Circulation. Cardiovascular Genetics
|August 19, 2010
PubMed

Insights

Genetic mutations in desmosomal proteins are a significant cause of dilated cardiomyopathy, a condition previously thought distinct from arrhythmogenic right ventricular cardiomyopathy. These findings expand the genetic understanding of heart failure.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic Basis of Cardiomyopathy

Background:

  • Idiopathic dilated cardiomyopathy (DCM) has a familial component, but its genetic underpinnings remain largely unknown.
  • Desmosomal protein genes, primarily linked to arrhythmogenic right ventricular cardiomyopathy (ARVC), are implicated in left ventricular dysfunction.
  • The role of desmosomal gene mutations in unselected DCM patients is not well-established.

Purpose of the Study:

  • To investigate the prevalence of mutations in five key desmosomal protein genes in patients diagnosed with dilated cardiomyopathy.
  • To assess the clinical significance and phenotypic presentation of desmosomal gene mutations in DCM.

Main Methods:

  • Conducted clinical evaluations, ECG, echocardiography, and exercise testing on 100 unrelated DCM patients.
  • Performed mutation screening for five desmosomal protein genes (plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, desmocollin-2).
  • Analyzed clinical phenotypes of patients with and without pathogenic desmosomal mutations.

Main Results:

  • Pathogenic mutations in desmosomal protein genes were identified in 5% of DCM patients.
  • Patients with desmosomal mutations showed a similar phenotype to non-carriers, except for a higher incidence of exercise-induced ventricular ectopy.
  • None of the mutation carriers met current ARVC diagnostic criteria, though one showed left ventricular fibrofatty changes post-mortem.

Conclusions:

  • Mutations in desmosomal protein genes can lead to both dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy.
  • These findings challenge the distinct clinicopathologic classification of DCM and ARVC.
  • Desmosomal gene mutations represent a common genetic cause underlying diverse cardiomyopathic phenotypes.
Abstract

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