Systematic examination of DNA variants in the parkin gene in patients with Parkinson's disease

摘要

Increasing evidence suggests that genetic factors play an important role in the pathogenesis of Parkinson's disease (PD). Three genes, namely α-synuclein, parkin, and UCH-L1, have been implicated in familial PD. An exon deletion in the parkin gene is the mutation most frequently mentioned in published data. The parkin gene was first identified by Japanese researchers, and, since fragment deletions in coding exons of this gene have been proven responsible for autosomal recessive juvenile parkinsonism (AR-JP), several follow-up reports from European groups have shown that point mutations in this gene also contribute to the pathogenesis of PD, especially early-onset PD. Further research has suggested that mutations in parkin may also be involved in sporadic PD (idiopathic PD ) . Japanese researchers have also identified 3 single nucleotide polymorphisms (SNPs) located in exon 4 (S/N 167) and exon 10 (R/W 366, V/L 380) . In China, several groups have additionally identified various mutations, including both deletions and point mutations, in Chinese patients with familial or sporadic PD. However, these investigations performed on Chinese subjects did not systematically examine all 12 exons of the parkin gene; only partial target exons of the parkin gene were examined. It is therefore necessary to perform a systematic study of DNA variations in the parkin gene. In the present study, we analyzed different mutations in parkin using a variety of molecular protocols, in order to explore the impact of parkin variants on the pathogenesis of sporadic PD in Han Chinese.