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

帕金森病（PD）是第二大最常见的神经退行性疾病，65岁以上人群的患病率为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。在我们的实验室中，我们发现了与常染色体隐性遗传性少年帕金森病（AR-JP）有关的帕金基因。此外，我们发现帕金作为一种泛素连接酶与泛素蛋白酶体途径直接相连。在我们的帕金基因突变分析中，我们研究的大约50%的患者没有帕金突变。因此，其余的帕金突变患者可能与1p35-36位点的PARK6或1p36位点的PARK7有关。最近，PINK1和DJ-1基因分别被鉴定为PARK6和PARK7的致病基因。在我们之前的研究中，对PARK6和PARK7的单倍型分析显示，一些日本患者可能存在PINK1或DJ-1突变的家族。因此，我们分析了其余无parkin突变患者的PINK1和DJ-1突变。随后，11名患者出现不同的新型PINK1突变。在我们广泛的研究中，我们发现了PINK1基因的缺失突变。总而言之，PINK1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。此外，我们还发现了几个家族没有突变的已知致病基因，如parkin， PINK1和DJ-1。部分遗传方式为常染色体隐性遗传，类型为晚发性帕金森病。我们正在开始确定一个新的位点和致病基因负责常染色体隐性晚发性帕金森病。

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.