Journal
CIRCULATION-CARDIOVASCULAR GENETICS
Volume 2, Issue 5, Pages 428-U36Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.109.858217
Keywords
arrhythmia; cardiomyopathy; ventricular tachycardia; sudden cardiac death; genetics; desmosome; ARVD/C
Funding
- National Institutes of Health [HL088072]
- France-Merrick Foundation
- Jeff Cooper CARE Foundation
- Stichting Dr Hendrik Muller's Vaderlandsch Fonds
- Van Wijck-Stam-Caspers fund
- Bogle Foundation
- Campanella family
- Wilmerding Endowment
- Healing Hearts Foundation
Ask authors/readers for more resources
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. (Circ Cardiovasc Genet. 2009;2:428-435.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available