Recurrent and founder mutations in the Netherlands: Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia

P. A. Van Der Zwaag, M. G.P.J. Cox, C. Van Der Werf, A. C.P. Wiesfeld, J. D.H. Jongbloed, D. Dooijes, H. Bikker, R. Jongbloed, A. J. H. Suurmeijer, M. P. Van Den Berg, R. M. W. Hofstra, R. N.W. Hauer, A. A.M. Wilde, J. P. Van Tintelen

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review


Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an inherited cardiac disease with reduced penetrance and a highly variable expression. Mutations in the gene encoding the plakophilin-2 gene (PKP2) are detected in about 50% of ARVC/D patients. The p.Arg79X mutation in PKP2 has been identified in Europe and North America and has been functionally characterised. We evaluated the prevalence of the p.Arg79X mutation in PKP2 in the Dutch population. Methods Twelve index patients and 41 family members were evaluated in three university hospitals in the Netherlands. The diagnosis of ARVC/D was established according to the recently revised Task Force Criteria. Segregation of the p.Arg79X mutation was studied and haplotypes were reconstructed to determine whether the p.Arg79X mutation was a recurrent or a founder mutation. Results The p.Arg79X mutation in PKP2 was identified in 12 index patients. Haplotype analysis revealed a shared haplotype among Dutch p.Arg79X mutation carriers, ndicating a common founder. Six index patients (50%) had a first- or second-degree relative who had died of sudden cardiac death below 40 years of age. At age 60, only 60% of the mutation carriers had experienced any symptoms. There was no significant difference in symptom-free survival and event-free survival between men and women. Conclusion We have identified the largest series of patients with the same desmosome gene mutation in ARVC/D reported to date. This p.Arg79X mutation in PKP2 is a founder mutation in the Dutch population. The phenotypes of PKP2 p.Arg79X mutation carriers illustrate the clinical variability and reduced penetrance often seen in ARVC/D. (Neth Heart J 2010;18:583-91.).

Original languageEnglish
Title of host publicationFounder Mutations in Inherited Cardiac Diseases in the Netherlands
PublisherBohn Stafleu Van Loghum bv
Number of pages11
ISBN (Electronic)9789036807050
ISBN (Print)9036807042, 9789036807043
Publication statusPublished - 1-Nov-2014


Dive into the research topics of 'Recurrent and founder mutations in the Netherlands: Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia'. Together they form a unique fingerprint.

Cite this