Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population†
Karen Nuytemans
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorBram Meeus
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorDavid Crosiers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorDirk Goossens
Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorSebastiaan Engelborghs
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorPhilippe Pals
Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorBarbara Pickut
Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorMarleen Van den Broeck
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorEllen Corsmit
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorPatrick Cras
Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorPeter P. De Deyn
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorJurgen Del-Favero
Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorCorresponding Author
Christine Van Broeckhoven
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Neurodegenerative Brain Diseases Group, VIB-Department of Molecular Genetics, University of Antwerp-CDE, Parking P4, Building V, Room 0.10, Universiteitsplein 1, B-2610 Antwerp, BelgiumSearch for more papers by this authorJessie Theuns
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorKaren Nuytemans
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorBram Meeus
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorDavid Crosiers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorNathalie Brouwers
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorDirk Goossens
Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorSebastiaan Engelborghs
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorPhilippe Pals
Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorBarbara Pickut
Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorMarleen Van den Broeck
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorEllen Corsmit
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorPatrick Cras
Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
Search for more papers by this authorPeter P. De Deyn
Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
Search for more papers by this authorJurgen Del-Favero
Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorCorresponding Author
Christine Van Broeckhoven
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Neurodegenerative Brain Diseases Group, VIB-Department of Molecular Genetics, University of Antwerp-CDE, Parking P4, Building V, Room 0.10, Universiteitsplein 1, B-2610 Antwerp, BelgiumSearch for more papers by this authorJessie Theuns
Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
University of Antwerp, Antwerp, Belgium
Search for more papers by this authorCommunicated by Mireille Claustres
Abstract
The relative contribution of simple mutations and copy number variations (CNVs) in SNCA, PARK2, PINK1, PARK7, and LRRK2 to the genetic etiology of Parkinson disease (PD) is still unclear because most studies did not completely analyze each gene. In a large group of Belgian PD patients (N=310) and control individuals (N=270), we determined the mutation frequency of both simple mutations and CNVs in these five PD genes, using direct sequencing, multiplex amplicon quantification (MAQ), and real-time PCR assays. Overall, we identified 14 novel heterozygous variants, of which 11 were absent in control individuals. We observed eight PARK2 (multiple) exon multiplications in PD patients and one exon deletion in a control individual. Furthermore, we identified one SNCA whole-gene duplication. The PARK2 and LRRK2 mutation frequencies in Belgian PD patients were similar to those reported in other studies. However, at this stage the true pathogenic nature of some heterozygous mutations in recessive genes remains elusive. Furthermore, though mutations is SNCA, PINK1, and PARK7 are rare, our identification of a SNCA duplication confirmed that screening of these genes remains meaningful. Hum Mutat 30:1–8, 2009. © 2009 Wiley-Liss, Inc.
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