Causative gene detection and its functional analysis for autosomal dominant Sagamihara Parkinsonism

常染色体显性相模原帕金森病致病基因检测及其功能分析

• 批准号: 16590843
• 负责人: HASEGAWA Kazuko
• 金额: $ 2.3万
• 依托单位: National Hospital Orgainzation, Sagamihara National Hospital, Clinical Research center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590843/
• 关键词: 家族性パーキンソン病; PARK8; LRRK2; DRDN; I2020T; familial Parkinsonisum

We detected a missense mutation in the LRRK2 gene in members of the Japanese family with autosomal dominant Parkingson's desease (PD) (Sagamihara family) on whose basis the PARK8 PD locus was originally defined. Thus, LRRK2 was concluded to be the gene responsible for PARK8. The mutation identified was located in the kinase domain and was identical to that reported in one of the PARK8-linked Caucasian families, suggesting that this mutation is essential for the pathogenesis. The unique pathological features of the Sagamihara family, characterized by pure nigral degeneration without Lewy bodies, provided us with a valuable oppotunity to elucidate the protein structure-pathogenesis relationship of the gene product of LRRK2.

我们检测到一个错义突变的LRRK 2基因在日本家庭成员的常染色体显性帕金森病（PD）（相模原家庭）的基础上，PARK 8 PD基因座最初被定义。因此，LRRK 2被认为是负责PARK 8的基因。所鉴定的突变位于激酶结构域中，并且与PARK 8连锁的高加索人家族中的一个报告的突变相同，这表明该突变对于发病机制是必需的。相模原家族独特的病理特征，其特征在于纯黑质变性而无路易体，这为我们阐明LRRK 2基因产物的蛋白质结构-致病关系提供了宝贵的机会。

项目成果

An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family

• DOI: 10.1002/ana.20484
• 发表时间: 2005-06-01
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Funayama, M;Hasegawa, K;Obata, F
• 通讯作者: Obata, F