title: Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.
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.
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.|Department of Pathology, Columbia University, New York, New York, USA.
authors.forename: Lorraine N
authors.initials: LN
authors.lastname: Clark
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
authors.forename: Shehla
authors.initials: S
authors.lastname: Afridi
authors.affiliation: Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Mejia-Santana
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Juliette
authors.initials: J
authors.lastname: Harris
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.|Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Elan D
authors.initials: ED
authors.lastname: Louis
authors.affiliation: Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Lucien J
authors.initials: LJ
authors.lastname: Cote
authors.affiliation: Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.|Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Andrews
authors.affiliation: Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Wavrant De-Vrieze
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.|Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.|Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Fahn
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Waters
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Blair
authors.initials: B
authors.lastname: Ford
authors.affiliation: Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Frucht
authors.affiliation: Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.|Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.|Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.|The Epidemiology of Brain Disorders Department, New York State Psychiatric Institute, New York, New York, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Ottman
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.|Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.|Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.|Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D003710:Demography; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D000071617:Protein Deglycase DJ-1
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1