Comprehensive desmosome mutation analysis in north americans with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • den Haan, AD; Tan, BY; Zikusoka, MN; Lladó, LI; Jain, R; Daly, A; Tichnell, C; James, C; Amat-Alarcon, N; Abraham, T; Russell, SD; Bluemke, DA; Calkins, H; Dalal, D; Judge, DP

Published Date

  • October 2009

Published In

Volume / Issue

  • 2 / 5

Start / End Page

  • 428 - 435

PubMed ID

  • 20031617

Pubmed Central ID

  • 20031617

Electronic International Standard Serial Number (EISSN)

  • 1942-3268

Digital Object Identifier (DOI)

  • 10.1161/CIRCGENETICS.109.858217

Language

  • eng

Conference Location

  • United States