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Screening of genes encoding junctional candidates in arrhythmogenic right ventricular cardiomyopathy/dysplasia

Estelle Gandjbakhch1, Alexia Vite, Françoise Gary

  • 1UPMC Univ Paris 6, INSERM, UMRS 956, AP-HP, 91 Boulevard de l'Hôpital, Paris F-75013, France.

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology
|July 17, 2013
PubMed

Insights

Genetic analysis of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) did not reveal mutations in candidate genes or PKP2 3'-UTR. Rare variants in PKP4 and PERP warrant further investigation for their role in ARVC/D.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Cardiology
  • Genetic basis of inherited cardiomyopathies

Background:

  • Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited heart condition.
  • Fibro-fatty tissue replaces the right ventricle, leading to arrhythmias.
  • Known genetic causes, primarily desmosomal genes, explain only about 50% of ARVC/D cases.

Purpose of the Study:

  • To identify novel genetic causes of ARVC/D.
  • Focused on the 3 -untranslated region (UTR) of the PKP2 gene and other desmosomal genes.
  • Investigated candidate genes for their role in ARVC/D pathogenesis.

Main Methods:

  • Screened 64 ARVC/D patients lacking mutations in known desmosomal genes.
  • Analyzed the PKP2 3 -UTR and coding sequences of PNN, CTNNA3, CAV1, and PLN.
  • Utilized a candidate gene approach for genetic variant identification.

Main Results:

  • No mutations were found in the PKP2 3 -UTR or the coding regions of other candidate genes.
  • Two rare heterozygous missense variants (p.Gly59Arg in PERP and p.Asp604Gly in PKP4) were identified in one patient.
  • These variants affect evolutionarily conserved residues and have a low minor allele frequency.

Conclusions:

  • Mutations in the investigated candidate genes are unlikely to be major causes of ARVC/D.
  • 3 -UTR mediated regulation of PKP2 mRNA does not appear to be a significant factor in this ARVC/D cohort.
  • Further research is necessary to determine the potential role of rare PKP4 and PERP variants in ARVC/D.
Abstract

Keywords:
Arrhythmogenic right ventricular cardiomyopathy/dysplasiaCandidate gene analysisCardiomyopathyDesmosomesGeneticsMutation

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