Pathogenicity of the Lrrk2 R1514Q substitution in Parkinson's disease

Authors

  • Mathias Toft,

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
    2. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
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    • The first two authors contributed equally to this study.

  • Ignacio F. Mata,

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
    2. Laboratorio de Genetica Molecular, Instituto de Investigacion Nefrologica (IRSIN-FRIAT), Hospital Universitario Central de Asturias, Oviedo, Spain
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    • The first two authors contributed equally to this study.

  • Owen A. Ross,

    Corresponding author
    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
    • Molecular Genetics Laboratory and Core, Morris K. Udall Parkinson's Disease Research Center of Excellence, Mayo Clinic, Department of Neuroscience, 4500 San Pablo Road, Jacksonville, FL 32224
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  • Jennifer Kachergus,

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
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  • Mary M. Hulihan,

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
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  • Kristoffer Haugarvoll,

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
    2. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
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  • Jeremy T. Stone,

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
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  • Marta Blazquez,

    1. Servicio de Neurología, Hospital Universitario Central de Asturias, Oviedo, Spain
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  • J. Mark Gibson,

    1. Department of Neurology, Royal Victoria Hospital, Belfast, Ireland
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  • Jan O. Aasly,

    1. Department of Neurology, St. Olav's Hospital, Trondheim, Norway
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  • Linda R. White,

    1. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
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  • Timothy Lynch,

    1. Department of Neurology, Mater Misericordiae Hospital, Dublin, and University College Dublin Conway Neuroscience Investigator, Dublin, Ireland
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  • Charles H. Adler MD, PhD,

    1. Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Katrina Gwinn-Hardy,

    1. Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Matthew J. Farrer

    1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, Florida, USA
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Abstract

An increasing number of nonsynonymous LRRK2 variants are being reported as putative pathogenic mutations. We identified one large kindred harboring the Lrrk2 R1514Q substitution; however, the variant did not segregate fully with disease. Combined analyses of three case–control series demonstrate that the R1514Q substitution is not associated with increased risk of disease (OR: 1.3; 95% CI: 0.6–2.8; P = 0.45). These findings highlight the importance of using family-based studies and multiple population screenings when examining the association of these polymorphic LRRK2 gene variants with Parkinson's disease. © 2007 Movement Disorder Society

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