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

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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.