TY - JOUR
T1 - Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations
AU - Elfferich, Peter
AU - Verleun-Mooijman, Marja C.
AU - Maat-Kievit, J. Anneke
AU - Van De Warrenburg, Bart P.C.
AU - Abdo, Wilson F.
AU - Eshuis, Sylvia A.
AU - Leenders, Klaus L.
AU - Hovestadt, Ad
AU - Zijlmans, Jan C.M.
AU - Stroy, Jan Pieter M.
AU - Van Swieten, John C.
AU - Boon, Agnita J.W.
AU - Van Engelen, Klaartje
AU - Verschuuren-Bemelmans, Corien C.
AU - Lesnik-Oberstein, Saskia A.J.
AU - Tassorelli, Cristina
AU - Lopiano, Leonardo
AU - Bonifati, Vincenzo
AU - Dooijes, Dennis
AU - Van Minkelen, Rick
N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Breakpoint mapping
KW - Common founder
KW - Deletion
KW - Duplication
KW - Parkin
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84855274634&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s10048-011-0302-9
DO - https://doi.org/10.1007/s10048-011-0302-9
M3 - Article
C2 - 21993715
SN - 1364-6745
VL - 12
SP - 263
EP - 271
JO - Neurogenetics
JF - Neurogenetics
IS - 4
ER -