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Parkinson's disease and LRRK2: Frequency of a common mutation in U.S. movement disorder clinics

Authors

  • Denise M. Kay PhD,

    1. Genomics Institute, Wadsworth Center, New York State Department of Health, Albany, New York, USA
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  • Cyrus P. Zabetian MS, MD,

    1. Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Stewart A. Factor DO,

    1. Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York, USA
    2. Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA
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  • John G. Nutt MD,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
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  • Ali Samii MD,

    1. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
    2. Parkinson's Disease Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, USA
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  • Alida Griffith MD,

    1. Booth Gardner Parkinson's Care Center, Evergreen Hospital Medical Center, Kirkland, Washington, USA
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  • Tom D. Bird MD,

    1. Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, USA
    2. Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA
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  • Patricia Kramer PhD,

    1. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
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  • Donald S. Higgins MD,

    1. Parkinson's Disease and Movement Disorder Clinic, Albany Medical Center, Albany, New York, USA
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  • Haydeh Payami PhD

    Corresponding author
    1. Genomics Institute, Wadsworth Center, New York State Department of Health, Albany, New York, USA
    2. Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA
    • Genomics Institute, Wadsworth Center, New York State Department of Health, P.O. Box 22002, Albany, NY 12201

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Abstract

The G2019S mutation in the LRRK2 gene is reportedly a common cause of familial Parkinson's disease (PD) and may also have a significant role in nonfamilial PD. The objective of this study was to assess mutation carrier frequency in PD patients from movement disorder clinics in the United States, stratified by family history, age at onset, and geography; to determine carrier frequency in a large and well-characterized control population; to examine segregation of mutation in families of patients; and to correlate genotype with clinical phenotype. One thousand four hundred twenty-five unrelated PD patients from movement disorder clinics in Oregon, Washington, and New York and 1,647 unrelated controls were studied. The G2019S mutation was detected using a TaqMan assay and verified by sequencing. Eighteen of 1,425 patients and one of 1,647 controls had the mutation. Carrier frequency (± 2SE) in patients was 0.013 ± 0.006 overall, 0.030 ± 0.019 in familial PD, 0.007 ± 0.005 in nonfamilial PD, 0.016 ± 0.013 in early-onset PD, and 0.012 ± 0.007 in late-onset PD. Geographic differences were insignificant. Age at onset of mutation carriers ranged from 28 to 71 years. Mutation carriers were clinically indistinguishable from idiopathic PD. LRRK2 G2019S is the single most common pathogenic mutation linked to neurodegenerative disease to date. © 2005 Movement Disorder Society

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