DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease
DJ-1 (PARK7) mutations are less frequent than Parkin (PARK2) mutations in early-onset Parkinson disease
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DOI：
10.1212/01.wnl.0000113022.51739.88
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发表时间：
2004-02-10
期刊：
影响因子：
9.9
通讯作者：
Klein, C
中科院分区：
文献类型：
--
作者：
Hedrich, K;Djarmati, A;Klein, C
背景：帕金森氏基因（PARK2）突变是隐性遗传早发性帕金森氏病（EOPD）最常见的原因，但仅占部分病例。DJ-1 （PARK7）是最近报道的第二个与隐性遗传PD相关的基因，在两个家族中具有纯合外显子缺失和纯合点突变。方法：为了研究DJ-1突变的频率，作者对100例EOPD患者的DJ-1的所有6个编码外显子进行了突变分析。为了检测外显子重排，作者开发了一种定量双工PCR法。变性高效液相色谱分析用于筛选点突变和小缺失。此外，如前所述进行帕金分析。结果：作者发现了两个单一杂合功能缺失的DJ-1突变的携带者，包括外显子5至7的杂合缺失和11碱基对的缺失，删除了内含子5的不变供体剪接位点。有趣的是，本研究中发现的两种DJ-1突变仅在杂合状态下发现。作者还在患者和对照组的1.5%的染色体中检测到多态性（R98Q）。在相同的患者样本中，17例检测到帕金基因突变。结论：在EOPD患者中，DJ-1基因突变的频率低于Parkin基因突变，但应被认为是EOPD的可能原因。DJ-1单杂合突变对黑质纹状体系统的影响，如Parkin和PARK6的杂合变化，仍有待阐明。
Background: Mutations in the Parkin gene (PARK2) are the most commonly identified cause of recessively inherited early-onset Parkinson disease (EOPD) but account for only a portion of cases. DJ-1 (PARK7) was recently reported as a second gene associated with recessively inherited PD with a homozygous exon deletion and a homozygous point mutation in two families. Methods: To investigate the frequency of DJ-1 mutations, the authors performed mutational analysis of all six coding exons of DJ-1 in 100 EOPD patients. For the detection of exon rearrangements, the authors developed a quantitative duplex PCR assay. Denaturing high performance liquid chromatography analysis was used to screen for point mutations and small deletions. Further, Parkin analysis was performed as previously described. Results: The authors identified two carriers of single heterozygous loss-of-function DJ-1 mutations, including a heterozygous deletion of exons 5 to 7 and an 11-base pair deletion, removing the invariant donor splice site in intron 5. Interestingly, both DJ-1 mutations identified in this study were found in the heterozygous state only. The authors also detected a polymorphism (R98Q) in 1.5% of the chromosomes in both the patient and control group. In the same patient sample, 17 cases were detected with mutations in the Parkin gene. Conclusions: Mutations in DJ-1 are less frequent than mutations in Parkin in EOPD patients but should be considered as a possible cause of EOPD. The effect of single heterozygous mutations in DJ-1 on the nigrostriatal system, as described for heterozygous changes in Parkin and PARK6, remains to be elucidated.