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

被引:55
作者
Clark, LN
Afridi, S
Mejia-Santana, H
Harris, J
Louis, ED
Cote, LJ
Andrews, H
Singleton, A
De-Vrieze, FW
Hardy, J
Mayeux, R
Fahn, S
Waters, C
Ford, B
Frucht, S
Ottman, R
Marder, K
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA
[2] New York State Psychiat Inst & Hosp, Epidemiol Brain Disorders Dept, New York, NY 10032 USA
[3] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA
[4] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA
[5] NIA, Mol Genet Sect, NIH, Bethesda, MD 20892 USA
[6] Columbia Univ, Coll Phys & Surg, Dept Epidemiol, New York, NY 10032 USA
[7] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA
[8] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10032 USA
[9] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA
关键词
Parkinson's disease; DJ-1; mutations; early onset; multiethnic cohort;
D O I
10.1002/mds.20131
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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-by deletion spanning exons l 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. (C) 2004 Movement Disorder Society.
引用
收藏
页码:796 / 800
页数:5
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