Comprehensive desmosome mutation analysis in North Americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy

A. Dénise Den Haan, Boon Yew Tan, Michelle N. Zikusoka, Laura Ibañez Lladó, Rahul Jain, Amy Daly, Crystal Tichnell, Cynthia James, Nuria Amat-Alarcon, Theodore Abraham, Stuart D. Russell, David A. Bluemke, Hugh Calkins, Darshan Dalal, Daniel P. Judge

Research output: Contribution to journalArticlepeer-review

Abstract

Background-Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited disorder typically caused by mutations in components of the cardiac desmosome. The prevalence and significance of desmosome mutations among patients with ARVD/C in North America have not been described previously. We report comprehensive desmosome genetic analysis for 100 North Americans with clinically confirmed or suspected ARVD/C. Methods and Results-In 82 individuals with ARVD/C and 18 people with suspected ARVD/C, DNA sequence analysis was performed on PKP2, DSG2, DSP, DSC2, and JUP. In those with ARVD/C, 52% harbored a desmosome mutation. A majority of these mutations occurred in PKP2. Notably, 3 of the individuals studied have a mutation in more than 1 gene. Patients with a desmosome mutation were more likely to have experienced ventricular tachycardia (73% versus 44%), and they presented at a younger age (33 versus 41 years) compared with those without a desmosome mutation. Men with ARVD/C were more likely than women to carry a desmosome mutation (63% versus 38%). A mutation was identified in 5 of 18 patients (28%) with suspected ARVD. In this smaller subgroup, there were no significant phenotypic differences identified between individuals with a desmosome mutation compared with those without a mutation. Conclusions-Our study shows that in 52% of North Americans with ARVD/C a mutation in one of the cardiac desmosome genes can be identified. Compared with those without a desmosome gene mutation, individuals with a desmosome gene mutation had earlier-onset ARVD/C and were more likely to have ventricular tachycardia.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalCirculation: Cardiovascular Genetics
Volume2
Issue number5
DOIs
StatePublished - Oct 2009

Keywords

  • Arrhythmia
  • Cardiomyopathy
  • Genetics
  • Sudden cardiac death
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Genetics
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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