Analysis of an early-onset Parkinson's disease cohort for DJ-1 mutations.
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.
Clark
Lorraine N
LN
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.
Afridi
Shehla
S
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Mejia-Santana
Helen
H
Gertrude H. Sergievsky Center, Columbia University, New York, New York, USA.
Harris
Juliette
J
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Louis
Elan D
ED
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.
Cote
Lucien J
LJ
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.
Andrews
Howard
H
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.
Singleton
Andrew
A
Molecular Genetics Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Wavrant De-Vrieze
Fabienne
F
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Hardy
John
J
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Mayeux
Richard
R
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.
Fahn
Stanley
S
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Waters
Cheryl
C
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Ford
Blair
B
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Frucht
Steven
S
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York, USA.
Ottman
Ruth
R
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.
Marder
Karen
K
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.
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
D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1