Mitsuyama Susumu, Ohtsubo Masafumi, Minoshima Shinsei, Shimizu Nobuyoshi
Laboratory of Gene Medicine, Keio University School of Medicine.
Department of Photomedical Genomics, Basic Medical Photonics Laboratory, Medical Photonics Research Center, Hamamatsu University School of Medicine.
Hum Mutat. 2015 Aug;36(8):E2430-40. doi: 10.1002/humu.22803. Epub 2015 Jun 3.
We previously isolated PARKIN (PARK2) as a gene responsible for a unique sort of Parkinson disease, namely Autosomal Recessive Juvenile Parkinsonism (ARJP). In this study, we surveyed all the available literature describing PARK2 gene/Parkin protein mutations found in Parkinson disease patients. Only carefully evaluated data were deposited in the graphical database MutationView (http://mutview.dmb.med.keio.ac.jp) to construct KM-parkin-DB, an independent sub-set database. Forty-four articles were selected for data curation regarding clinical information such as ethnic origins, manifested symptoms, onset age, and hereditary patterns as well as mutation details including base changes and zygosity. A total of 366 cases were collected from 39 ethnic origins and 96 pathogenic mutations were found. PARK2 gene mutations were found also in some general Parkinson disease patients. The majority (63%) of mutations in PARK2 were restricted to two particular domains (UBL and RING1) of the Parkin protein. In these domains, two major mutations, a large deletion (DelEx3) and a point mutation (p.Arg275Trp), were located.
我们之前分离出了PARKIN（PARK2）基因，它是导致一种特殊类型帕金森病（即常染色体隐性青少年帕金森综合征，ARJP）的基因。在本研究中，我们查阅了所有描述帕金森病患者中发现的PARK2基因/Parkin蛋白突变的文献。只有经过仔细评估的数据被存入图形数据库MutationView（http://mutview.dmb.med.keio.ac.jp），以构建独立的子集数据库KM-parkin-DB。我们选择了44篇文章进行数据整理，内容涉及种族起源、表现症状、发病年龄和遗传模式等临床信息，以及包括碱基变化和纯合度在内的突变细节。总共从39个种族中收集了366个病例，并发现了96个致病突变。在一些普通帕金森病患者中也发现了PARK2基因突变。PARK2基因的大多数突变（63%）局限于Parkin蛋白的两个特定结构域（UBL和RING1）。在这些结构域中，发现了两个主要突变，一个大的缺失（DelEx3）和一个点突变（p.Arg275Trp）。
