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Gepubliceerd in: Netherlands Heart Journal 12/2010

01-11-2010 | Original Article

Recurrent and founder mutations in the Netherlands

Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia

Auteurs: 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

Gepubliceerd in: Netherlands Heart Journal | Uitgave 12/2010

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Abstract

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, indicating 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.)
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Metagegevens
Titel
Recurrent and founder mutations in the Netherlands
Plakophilin-2 p.Arg79X mutation causing arrhythmogenic right ventricular cardiomyopathy/dysplasia
Auteurs
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
Publicatiedatum
01-11-2010
Uitgeverij
Bohn Stafleu van Loghum
Gepubliceerd in
Netherlands Heart Journal / Uitgave 12/2010
Print ISSN: 1568-5888
Elektronisch ISSN: 1876-6250
DOI
https://doi.org/10.1007/s12471-010-0839-5