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

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 bre...

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Bibliographic Details
Published in:Neurogenetics 2011-11, Vol.12 (4), p.263-271
Main Authors: Elfferich, Peter, Verleun-Mooijman, Marja C., Maat-Kievit, J. Anneke, van de Warrenburg, Bart P. C., Abdo, Wilson F., Eshuis, Sylvia A., Leenders, Klaus L., Hovestadt, Ad, Zijlmans, Jan C. M., Stroy, Jan-Pieter M., van Swieten, John C., Boon, Agnita J. W., van Engelen, Klaartje, Verschuuren-Bemelmans, Corien C., Lesnik-Oberstein, Saskia A. J., Tassorelli, Cristina, Lopiano, Leonardo, Bonifati, Vincenzo, Dooijes, Dennis, van Minkelen, Rick
Format: Article
Language:English
Subjects:
Adolescent
Adult
Age
Age of Onset
Aged
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Breakpoints
Chromosome aberrations
Chromosome Breakpoints
Chromosome Mapping
Classical genetics, quantitative genetics, hybrids
DNA Mutational Analysis
DNA probes
Exons
Female
Founder effect
Fundamental and applied biological sciences. Psychology
Gene Deletion
Gene Duplication
Gene mapping
Genetics of eukaryotes. Biological and molecular evolution
Genomics
Haplotypes
Human
Human Genetics
Humans
Male
Medical genetics
Medical sciences
Middle Aged
Molecular and cellular biology
Molecular Medicine
Movement disorders
Mutation
Neurodegenerative diseases
Neurons
Neurosciences
Original
Original Article
Parkin protein
Parkinson Disease - genetics
Parkinson's disease
Pedigree
Polymerase chain reaction
Polymerase Chain Reaction - methods
Ubiquitin-Protein Ligases - genetics
Vertebrates: nervous system and sense organs
Young Adult
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Summary: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 .
ISSN:1364-6745
1364-6753
DOI:10.1007/s10048-011-0302-9