Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations

Peter Elfferich, Marja C. Verleun-Mooijman, J. Anneke Maat-Kievit, Bart P.C. Van De Warrenburg, Wilson F. Abdo, Sylvia A. Eshuis, Klaus L. Leenders, Ad Hovestadt, Jan C.M. Zijlmans, Jan Pieter M. Stroy, John C. Van Swieten, Agnita J.W. Boon, Klaartje Van Engelen, Corien C. Verschuuren-Bemelmans, Saskia A.J. Lesnik-Oberstein, Cristina Tassorelli, Leonardo Lopiano, Vincenzo Bonifati, Dennis Dooijes, Rick Van Minkelen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Early-onset Parkinson's disease (EOPD) has been associated with recessive mutations in parkin (PARK2). About half of the mutations found in parkin are genomic rearrangements, i.e., large deletions or duplications. Although many different rearrangements have been found in parkin before, the exact breakpoints involving these rearrangements are rarely mapped. In the present study, the exact breakpoints of 13 different parkin deletions/duplications, detected in 13 patients out of a total screened sample of 116 EOPD patients using Multiple Ligation Probe Amplification (MLPA) analysis, were mapped using real time quantitative polymerase chain reaction (PCR), long-range PCR and sequence analysis. Deletion/duplication-specific PCR tests were developed as a rapid and low cost tool to confirmMLPA results and to test family members or patients with similar parkin deletions/duplications. Besides several different deletions, an exon 3 deletion, an exon 4 deletion and an exon 7 duplication were found in multiple families. Haplotype analysis in four families showed that a common haplotype of 1.2 Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3 Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin.

Original languageEnglish
Pages (from-to)263-271
Number of pages9
JournalNeurogenetics
Volume12
Issue number4
DOIs
Publication statusPublished - Nov 2011

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