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Molecular genetics of arrhythmogenic right ventricular cardiomyopathy: emerging horizon?

van Tintelen, J Petera; Hofstra, Robert MWa; Wiesfeld, Ans CPb; van den Berg, Maarten Pb; Hauer, Richard NWc; Jongbloed, Jan DHa

Current Opinion in Cardiology: May 2007 - Volume 22 - Issue 3 - p 185–192
doi: 10.1097/HCO.0b013e3280d942c4
Molecular genetics

Purpose of review Recent developments in the elucidation of genes underlying arrhythmogenic right ventricular cardiomyopathy and possible pathogenic mechanisms will be highlighted.

Recent findings The cardiac desmosome is a multiprotein structure involved in cell–cell interactions. Mutations in genes encoding desmosomal proteins such as PKP2, DSP, JUP, DSC2 and DSG2 underlie arrhythmogenic right ventricular cardiomyopathy, which can therefore be considered a desmosome cardiomyopathy. Mutations in the plakophilin-2 gene are most prevalent. Current pathophysiological insights suggest a final common pathway in which plakoglobin release from the desmosome, independent of the primarily affected desmosomal protein, results in desmosome impairment, intercalated disc remodeling and Wnt/β-catenin pathway signaling defects. The recognition of left ventricular involvement associated with mutations in desmosomal protein genes and low penetrance suggests that formal criteria should not be followed too closely in selecting patients for DNA analysis, because finding a mutation may have important implications for clinical practice.

Summary Recent developments have demonstrated that arrhythmogenic right ventricular cardiomyopathy can be considered a desmosome cardiomyopathy. Left ventricular involvement is not uncommon in this type of cardiomyopathy. Such findings are important for diagnostics and family screening and form a starting-point for the elucidation of other (non)-genetic factors influencing disease progression and outcome.

aDepartments of Genetics, the Netherlands

bCardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

cDepartment of Cardiology, Heart–Lung Center Utrecht, University Medical Center, Utrecht, the Netherlands

Correspondence to J. Peter van Tintelen, MD, Department of Genetics, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, the Netherlands Tel: +31 50 361 7223; fax: +31 50 361 7231; e-mail:

© 2007 Lippincott Williams & Wilkins, Inc.