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  • Open Access

Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update

Authors

  • Karen Nuytemans,

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

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

    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium
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  • Christine Van Broeckhoven

    Corresponding author
    1. Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium
    2. Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Antwerpen, Belgium
    • Neurodegenerative Brain Diseases Group, VIB, Department of Molecular Genetics, University of Antwerp, CDE, Universiteitsplein 1, B-2610 Antwerpen, Belgium
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  • Communicated by Richard G. H. Cotton

Abstract

To date, molecular genetic analyses have identified over 500 distinct DNA variants in five disease genes associated with familial Parkinson disease; α-synuclein (SNCA), parkin (PARK2), PTEN-induced putative kinase 1 (PINK1), DJ-1 (PARK7), and Leucine-rich repeat kinase 2 (LRRK2). These genetic variants include ∼82% simple mutations and ∼18% copy number variations. Some mutation subtypes are likely underestimated because only few studies reported extensive mutation analyses of all five genes, by both exonic sequencing and dosage analyses. Here we present an update of all mutations published to date in the literature, systematically organized in a novel mutation database (http://www.molgen.ua.ac.be/PDmutDB). In addition, we address the biological relevance of putative pathogenic mutations. This review emphasizes the need for comprehensive genetic screening of Parkinson patients followed by an insightful study of the functional relevance of observed genetic variants. Moreover, while capturing existing data from the literature it became apparent that several of the five Parkinson genes were also contributing to the genetic etiology of other Lewy Body Diseases and Parkinson-plus syndromes, indicating that mutation screening is recommendable in these patient groups. Hum Mutat 31:763–780, 2010. © 2010 Wiley-Liss, Inc.

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