Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations

Authors

  • Lorraine N. Clark PhD,

    Corresponding author
    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
    2. Department of Pathology, Columbia University, New York, New York, USA
    • Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032
    Search for more papers by this author
  • Shehla Afridi MSc,

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Helen Mejia-Santana MSc,

    1. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Juliette Harris PhD,

    1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Elan D. Louis MD, MS,

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
    2. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Lucien J. Cote MD,

    1. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    2. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Howard Andrews PhD,

    1. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    2. Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Andrew Singleton PhD,

    1. Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Search for more papers by this author
  • Fabienne Wavrant De-Vrieze PhD,

    1. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Search for more papers by this author
  • John Hardy PhD,

    1. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA
    Search for more papers by this author
  • Richard Mayeux MD, MSc,

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
    2. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    4. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Stanley Fahn MD,

    1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Cheryl Waters MD, FRCP,

    1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Blair Ford MD, FRCP,

    1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Steven Frucht MD,

    1. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author
  • Ruth Ottman PhD,

    1. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    2. Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    3. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    4. The Epidemiology of Brain Disorders Department, New York State Psychiatric Institute, New York, New York, USA
    Search for more papers by this author
  • Karen Marder MD, MPH

    1. Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA
    2. Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA
    3. Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    4. Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA
    Search for more papers by this author

Abstract

The frequency and relative contribution of DJ-1 mutations in early-onset Parkinson's disease (EOPD) is currently unknown. We analyzed a cohort of 89 EOPD patients (mean age at onset of PD ± SD, 41.5 ± 7.2 years), ascertained independent of family history, who participated in a study of the genetic epidemiology of PD. This study includes sequence analysis of the DJ-1 gene in addition to assaying the 14,082-bp deletion spanning exons 1 to 5, previously identified in a Dutch kindred, in 89 EOPD cases. A heterozygous missense mutation in exon 5 (A104T) was identified in an EOPD case of Asian ethnicity; this sequence variant was absent in 308 control chromosomes. We identified additional sequence variation in the DJ-1 gene, including a polymorphism in the coding region in exon 5 (R98Q), three polymorphisms in the 5′ untranslated region (exon 1A/1B), and two polymorphisms in intronic regions (IVS1 and IVS5). Mutations in the DJ-1 gene are rare in EOPD in both sporadic and familial cases. © 2004 Movement Disorder Society

Ancillary