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Heart Rhythm. 2011 Aug;8(8):1214-21. doi: 10.1016/j.hrthm.2011.03.015. Epub 2011 Mar 10.

Population-prevalent desmosomal mutations predisposing to arrhythmogenic right ventricular cardiomyopathy.

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  • 1Research Program for Molecular Medicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.

Abstract

BACKGROUND:

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive myocardial disorder caused by mutations of desmosomal cell adhesion proteins. The prevalence of these variants in the general population is unknown.

OBJECTIVE:

This study examined the spectrum and population prevalence of desmosomal mutations predisposing to ARVC in Finland.

METHODS:

We screened 29 Finnish ARVC probands for mutations in the DSP, DSG2, and DSC2 genes. All Finnish-type ARVC-associated mutations, including those 3 previously identified in PKP2 in the same patient group, were analyzed in the population-based Health 2000 cohort of 6,334 individuals and tested for association with electrocardiographic variables.

RESULTS:

We detected 2 novel mutations: DSG2 3059_3062delAGAG and DSP T1373A. DSG2 3059_3062delAGAG was present in a family with 5 mutation carriers. The endomyocardial samples of the DSG2 deletion carrier showed reduced immunoreactive signal for desmoglein-2, plakophilin-2, plakoglobin, and desmoplakin. DSP T1373A was found in 1 proband with typical right ventricular disease and exercise-related ventricular tachycardia. In the population sample, the collective prevalence of all 5 mutations identified in the 29 ARVC patients (PKP2 Q62K, Q59L, N613K, DSG2 3059_3062delAGAG, and DSP T1373A) was 31 of 6,334 individuals, or 0.5%. The apparent founder mutation PKP2 Q59L is present in 0.3% of Finns and was previously shown to have an approximately 20% disease penetrance.

CONCLUSION:

One of 200 Finns carries a desmosomal mutation that may predispose to ARVC and its clinical sequelae. ARVC-associated mutations may thus be more prevalent in the population than expected based on the published ARVC prevalence data.

Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

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PMID:
21397041
[PubMed - indexed for MEDLINE]
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