Posts Tagged ‘University Medical Center Utrecht’

North Americans With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Genomics of Ventricular arrhythmias, A-Fib, Right Ventricular Dysplasia, Cardiomyopathy – Comprehensive Desmosome Mutation Analysis

Reporter: Aviva Lev-Ari, PhD, RN

Genomics of Ventricular arrhythmias, A-Fib, Right Ventricular Dysplasia, Cardiomyopathy – Comprehensive Desmosome Mutation Analysis in North Americans With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

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

Author Affiliations

From the Department of Medicine/Cardiology (A.D.d.H., B.Y.T., M.N.Z., L.I.L., R.J., A.D., C.T., C.J., N.A.-A., T.A., S.D.R., H.C., D.D., D.P.J.), Johns Hopkins University School of Medicine, Baltimore, Md; Department of Cardiology, Division of Heart and Lungs (A.D.d.H.), University Medical Center Utrecht, Utrecht, The Netherlands; and National Institutes of Health, Radiology and Imaging Sciences (D.A.B.), Bethesda, Md.

Correspondence to Daniel P. Judge, MD, Johns Hopkins University, Division of Cardiology, Ross 1049; 720 Rutland Avenue, Baltimore, MD 21205. E-mail djudge@jhmi.edu


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.


Circulation: Cardiovascular Genetics.2009; 2: 428-435

Published online before print June 3, 2009,

doi: 10.1161/ CIRCGENETICS.109.858217


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