The role of pathogenic DJ-1 mutations in Parkinson's disease
The role of pathogenic DJ-1 mutations in Parkinson's disease
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DOI：
10.1002/ana.10675
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发表时间：
2003-09-01
影响因子：
11.2
通讯作者：
Wood, NW
中科院分区：
文献类型：
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作者：
Abou-Sleiman, PM;Healy, DG;Wood, NW
在两个早发型帕金森病（YOPD）的近亲家族中发现了DJ-1 （PARK7）突变。本研究旨在证实致病性DJ-1突变的存在，并确定其在年轻发病和更典型的晚发病帕金森病（PD）中的作用。通过直接测序，对185名不相关的YOPD患者和190例病理证实的PD患者进行了DJ-1基因的整个开放阅读框筛选。筛选种族匹配的对照，以确定所有突变。我们报告了在我们的患者队列中致病性DJ-1突变的低频率。在两个YOPD样本中发现一个纯合错义突变和一个杂合突变。此外，在该基因的编码序列中发现了几个变体，这些变体可能代表多态性。在一种情况下，多态性是群体特有的。报告的14Kbp缺失未在我们的任何样本或对照中发现。我们确认在YOPD中存在致病性DJ-1突变，并估计其频率约为1%。在我们的发病较晚的散发性病理确诊病例队列中未发现突变，这表明DJ-1突变可能只是很少导致这种更典型的散发性疾病。
Mutations in DJ-1 (PARK7) have been reported in two consanguineous families with young-onset Parkinson's disease (YOPD). This study aims to confirm the presence of pathogenic DJ-1 mutations and determine their contribution in young-onset and more typical later onset Parkinson's disease (PD). The entire open reading frame of the DJ-1 gene was screened by direct sequencing in 185 unrelated YOPD patients and a separate cohort of 190 pathologically proven cases of PD. Ethnically matched controls were screened for all mutations identified. We report a low frequency of pathogenic DJ-1 mutations in our cohort of patients. One homozygous missense mutation and one heterozygous mutation were found in two YOPD samples. In addition, several variants were found in the coding sequence of the gene, which are likely to represent polymorphisms. In one case, the polymorphism was population specific. The reported 14Kbp deletion was not found in any of our samples or controls. We confirm the presence of pathogenic DJ-1 mutations in YOPD and estimate their frequency at approximately 1%. No mutations were found in our cohort of later onset sporadic pathologically confirmed cases, suggesting that DJ-1 mutations may only rarely contribute to the cause of this more typical sporadic form of the disease.