PINK1 gene and DJ-1 gene mutation analysis about juvenile Parkinson's disease.

帕金森氏病(PD)是第二种最常见的神经退行性疾病，在65岁以上的人中患病率为1%。虽然大多数帕金森病病例是散发性的，但现在明确的是，遗传因素参与了帕金森氏病的发病。在我们实验室，我们发现了常染色体隐性遗传性青少年帕金森综合征(AR-JP)的parkin基因。此外，我们还发现Parkin作为一种泛素连接酶与泛素蛋白酶体途径直接相关。在我们的parkin基因突变分析中，我们研究的患者中约有50%没有parkin突变。因此，其余具有parkin突变的患者可能与映射到1p35-36的PARK6或映射到1p36的Park7连锁。最近，PINK1和DJ-1基因分别被确定为PARK6和Park7的致病基因。在我们之前的研究中，PARK6和Park7的单倍型分析表明，一些带有PINK1或DJ-1突变的家系可能发生在日本患者中。因此，我们分析了其余没有parkin突变的患者的PINK1和DJ-1突变。随后，11名患者出现了不同的新的PINK1突变。在我们的广泛研究中，我们发现了PINK1基因的一个缺失突变。综上所述，PINK1基因突变在常染色体隐性遗传性PD中的频率约为5%。与此相反的是，在日本患者中没有发现DJ-1突变。此外，我们还发现了几个已知致病基因没有突变的家族，如parkin、PINK1和DJ-1。部分患者遗传方式为常染色体隐性遗传，类型为晚发型帕金森病。我们开始发现常染色体隐性遗传性迟发性帕金森病的一个新的基因座和致病基因。

Parkinson's disease (PD) is the second most common neurodegenerative disorder with a prevalence of 1% in individuals older than 65 years of age. Although the majority of PD cases are sporadic, it is now clear that genetic factors contribute to the pathogenesis of PD. In our laboratory, we identified parkin gene responsible for autosomal recessive juvenile parkinsonism (AR-JP). Furthermore, we found that parkin is direct linked to ubiquitin proteasome pathway as a ubiquitin ligase. In our mutation analysis for parkin gene, approximately 50% of the patients we studied had no parkin mutations. Thus, the remaining patients with parkin mutations would be possible to be linked to PARK6 mapped to 1p35-36 or PARK7 mapped to 1p36. Recently, PINK1 and DJ-1 genes have identified as causative genes for PARK6 and PARK7, respectively. In our previous study, haplotype analysis for PARK6 and PARK7 showed some families with PINK1 or DJ-1 mutations may take place in Japanese patients. Therefore, we analyzed PINK1 and DJ-1 mutations for the remaining patients with no parkin mutations. Subsequently, 11 patients had different novel PINK1 mutations. In our extensive study, we found a deletion mutation in PINK1 gene. Taken together, the frequency of PINK1 mutations is approximately 5% in autosomal recessive PD. Opposing to that, no DJ-1 mutation was found in Japanese patients. We furthermore have found several families with no mutation of known causative genes such as parkin, PINK1, and DJ-1. The inheritance mode of some of them are autosomal recessive and the type of them is late onset of PD. We are starting to identify a novel locus and causative gene responsible for autosomal recessive late onset PD.