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Relative contribution of simple mutations vs. copy number variations in five Parkinson disease genes in the Belgian population

Authors

  • Karen Nuytemans,

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
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  • Bram Meeus,

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
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  • David Crosiers,

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
    4. Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
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  • Nathalie Brouwers,

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
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  • Dirk Goossens,

    1. Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. University of Antwerp, Antwerp, Belgium
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  • Sebastiaan Engelborghs,

    1. Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
    2. University of Antwerp, Antwerp, Belgium
    3. Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
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  • Philippe Pals,

    1. Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
    2. Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
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  • Barbara Pickut,

    1. Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
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  • Marleen Van den Broeck,

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
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  • Ellen Corsmit,

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
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  • Patrick Cras,

    1. Laboratory of Neurobiology, Institute Born-Bunge, Antwerp, Belgium
    2. University of Antwerp, Antwerp, Belgium
    3. Division of Neurology, University Hospital Antwerp, Antwerp, Belgium
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  • Peter P. De Deyn,

    1. Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, Antwerp, Belgium
    2. University of Antwerp, Antwerp, Belgium
    3. Memory Clinic and Department of Neurology, ZNA Middelheim, Antwerp, Belgium
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  • Jurgen Del-Favero,

    1. Applied Molecular Genomics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. University of Antwerp, Antwerp, Belgium
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  • Christine Van Broeckhoven,

    Corresponding author
    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. 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, Belgium
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  • Jessie Theuns

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerp, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium
    3. University of Antwerp, Antwerp, Belgium
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  • Communicated 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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