caa a22 4500 445364637 CHVBK 20180317142926.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s10048-011-0302-9 doi (NATIONALLICENCE)springer-10.1007/s10048-011-0302-9 Breakpoint mapping of 13 large parkin deletions/duplications reveals an exon 4 deletion and an exon 7 duplication as founder mutations [Elektronische Daten] [Peter Elfferich, Marja Verleun-Mooijman, J. Maat-Kievit, Bart van de Warrenburg, Wilson Abdo, Sylvia Eshuis, Klaus Leenders, Ad Hovestadt, Jan Zijlmans, Jan-Pieter Stroy, John van Swieten, Agnita Boon, Klaartje van Engelen, Corien Verschuuren-Bemelmans, Saskia Lesnik-Oberstein, Cristina Tassorelli, Leonardo Lopiano, Vincenzo Bonifati, Dennis Dooijes, Rick van Minkelen] 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 1.2Mb could be distinguished for the exon 7 duplication and a common haplotype of 6.3Mb for the deletion of exon 4. These findings suggest common founder effects for distinct large rearrangements in parkin. The Author(s), 2011 Parkinson's disease nationallicence parkin nationallicence Deletion nationallicence Duplication nationallicence Common founder nationallicence Breakpoint mapping nationallicence Elfferich Peter Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut Verleun-Mooijman Marja Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut Maat-Kievit J. Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut van de Warrenburg Bart Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands aut Abdo Wilson Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands aut Eshuis Sylvia Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands aut Leenders Klaus Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands aut Hovestadt Ad Department of Neurology, Meander Medical Center, Amersfoort, The Netherlands aut Zijlmans Jan Department of Neurology, Amphia Hospital Breda, Breda, The Netherlands aut Stroy Jan-Pieter Department of Neurology, Amphia Hospital Breda, Breda, The Netherlands aut van Swieten John Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands aut Boon Agnita Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands aut van Engelen Klaartje Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands aut Verschuuren-Bemelmans Corien Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut Lesnik-Oberstein Saskia Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands aut Tassorelli Cristina Institute IRCCS ‘Mondino', Pavia, Italy aut Lopiano Leonardo Department of Neuroscience, University of Turin, Turin, Italy aut Bonifati Vincenzo Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut Dooijes Dennis Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands aut van Minkelen Rick Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut neurogenetics Springer-Verlag 12/4(2011-11-01), 263-271 1364-6745 12:4<263 2011 12 10048 https://doi.org/10.1007/s10048-011-0302-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-011-0302-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Elfferich Peter Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Verleun-Mooijman Marja Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Maat-Kievit J. Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- van de Warrenburg Bart Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Abdo Wilson Department of Neurology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Eshuis Sylvia Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Leenders Klaus Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Hovestadt Ad Department of Neurology, Meander Medical Center, Amersfoort, The Netherlands aut NATIONALLICENCE 700 1- Zijlmans Jan Department of Neurology, Amphia Hospital Breda, Breda, The Netherlands aut NATIONALLICENCE 700 1- Stroy Jan-Pieter Department of Neurology, Amphia Hospital Breda, Breda, The Netherlands aut NATIONALLICENCE 700 1- van Swieten John Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Boon Agnita Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- van Engelen Klaartje Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands aut NATIONALLICENCE 700 1- Verschuuren-Bemelmans Corien Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands aut NATIONALLICENCE 700 1- Lesnik-Oberstein Saskia Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Tassorelli Cristina Institute IRCCS ‘Mondino', Pavia, Italy aut NATIONALLICENCE 700 1- Lopiano Leonardo Department of Neuroscience, University of Turin, Turin, Italy aut NATIONALLICENCE 700 1- Bonifati Vincenzo Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut NATIONALLICENCE 700 1- Dooijes Dennis Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands aut NATIONALLICENCE 700 1- van Minkelen Rick Department of Clinical Genetics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/4(2011-11-01), 263-271 1364-6745 12:4<263 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer