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

帕金森病（PD）是第二常见的神经退行性疾病，在65岁以上的人群中患病率为1%。虽然大多数PD病例是散发的，但现在很清楚遗传因素有助于PD的发病机制。我们在本实验室发现了常染色体隐性遗传性幼年型帕金森综合征（AR-JP）的parkin基因。此外，我们发现parkin作为泛素连接酶直接连接到泛素蛋白酶体途径。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，剩下的帕金突变患者可能与PARK 6（定位于1 p35 -36）或PARK 7（定位于1 p36）相关。最近，PINK 1和DJ-1基因分别被鉴定为PARK 6和PARK 7的致病基因。在我们之前的研究中，PARK 6和PARK 7的单倍型分析显示，一些具有PINK 1或DJ-1突变的家族可能发生在日本患者中。因此，我们分析了PINK 1和DJ-1突变的其余患者没有parkin突变。随后，11名患者出现了不同的新型PINK 1突变。在我们广泛的研究中，我们发现PINK 1基因的缺失突变。总的来说，PINK 1突变的频率在常染色体隐性PD中约为5%。与此相反，在日本患者中没有发现DJ-1突变。我们还发现了几个已知致病基因如parkin，PINK 1和DJ-1没有突变的家族。部分病例的遗传方式为常染色体隐性遗传，部分病例为晚发型PD。我们开始确定一个新的基因座和致病基因负责常染色体隐性迟发性帕金森病。

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.