title: Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations.
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 confirm MLPA 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.
authors: Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
authors: Peter
authors: P
authors: Elfferich
authors: Marja C
authors: MC
authors: Verleun-Mooijman
authors: J Anneke
authors: JA
authors: Maat-Kievit
authors: Bart P C
authors: BP
authors: van de Warrenburg
authors: Wilson F
authors: WF
authors: Abdo
authors: Sylvia A
authors: SA
authors: Eshuis
authors: Klaus L
authors: KL
authors: Leenders
authors: Ad
authors: A
authors: Hovestadt
authors: Jan C M
authors: JC
authors: Zijlmans
authors: Jan-Pieter M
authors: JP
authors: Stroy
authors: John C
authors: JC
authors: van Swieten
authors: Agnita J W
authors: AJ
authors: Boon
authors: Klaartje
authors: K
authors: van Engelen
authors: Corien C
authors: CC
authors: Verschuuren-Bemelmans
authors: Saskia A J
authors: SA
authors: Lesnik-Oberstein
authors: Cristina
authors: C
authors: Tassorelli
authors: Leonardo
authors: L
authors: Lopiano
authors: Vincenzo
authors: V
authors: Bonifati
authors: Dennis
authors: D
authors: Dooijes
authors: Rick
authors: R
authors: van Minkelen
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D056905:Chromosome Breakpoints; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D055815:Young Adult
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein