紀伊半島の神経難病多発地域住民の遺伝素因と環境要因の解析

疑难神经疾病多发纪伊半岛居民遗传倾向及环境因素分析

• 批准号: 11157212
• 负责人: 葛原 茂樹
• 金额: $ 0.83万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11157212/
• 关键词: 筋萎縮性側索硬化症; パーキンソニズム; 痴呆; 神経難病; タウ遺伝子; タウ蛋白

紀伊半島に多発する筋萎縮性側索硬化症(ALS)とパーキンソン痴呆複合(PDC)の特徴は,家族性発症率が高く(70%以上),中枢神経系にアルツハイマー神経原線維変化(NFT)が多発することである.我々は,ALS/PDCの12症例でタウ遺伝子解析を,剖検2例でタウ蛋白解析を行った.タウ遺伝子解析では,ALS/PDC12症例の血液白血球からゲノムDNAを抽出し,タウ遺伝子のすべてのエキソンをsingle strand conformation polymorphism(SSCP)解析でスクリーニングした.frontotemporal dementia and parkinsonism linked chromosome 17(FTDP-17)で遺伝子変異が明らかにされているエキソン9〜13については直接塩基配列決定法を行った.SSCP,直接塩基配列決定法ともに変異は認められなかった.タウ蛋白解析では,ALS/PDCの2症例の剖検凍結脳から分離精製したNFTのPHFタウをタウ抗体でimmunoblotした.脱リン酸化後のALS/PDCの異常タウは6種類すべてのisoformから構成されており,アルツハイマー病と同一パターンで,特定のisoformの異常増加や欠損は認められなかった.以上の所見から,紀伊半島のALS/PDCは,家族性tauopathyではあってもタウ遺伝子自体に一次的原因がある可能性は低いと考えた.

There is a high incidence of familial syndrome (more than 70%) and a high rate of familial syndrome (more than 70%). The central nervous system has multiple symptoms, such as myasthenia gravis (ALS), atrophic cord sclerosis (ALS), dementia, dysphagia, myopia, myopia, myopia, We reported 12 cases of ALS/PDC 's disease and 2 cases of protein analysis. In the case of ALS/PDC12 's disease, white blood cells were extracted from blood cells, DNA was extracted, and single strand conformation polymorphism (SSCP) was used to analyze blood leukocytes. Frontotemporal dementia and parkinsonism linked chromosome 17 (FTDP-17) was used to determine the number of white blood cells. Frontotemporal dementia and parkinsonism linked chromosome 17 (FTDP-17) was used to determine the number of cells. SSCP. The direct basis column determination method is based on the direct base allocation method. Protein analysis was performed in 2 cases of ALS/PDC. Results were isolated from semen, NFT, PHF, antibodies, immunoblot. After deacidizing, the ALS/PDC, isoform, and isoform will become abnormal, and the disease will be the same as that of the disease, and the specific isoform will not be affected. The reason for the above sighting, ALS/PDC, and familial tauopathy syndrome is that the possibility of autologous pregnancy is low.

项目成果

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Sasaki R：“两个不相关的日本先天性肌强直家族中的新型 CLCN1 突变”神经肌肉失调.. 587-592 (1999)。

Kokubo Y: "Accumulation of neurofilaments and SOD1-immunoreactive products in a patient wih familial amyotrophic lateral sclerosis with I113T SOD1 mutation"Arch. Neurol.. 56・12. 1506-1508 (1999)

Kokubo Y：“具有 I113T SOD1 突变的家族性肌萎缩侧索硬化症患者中神经丝和 SOD1 免疫反应产物的积累”Arch. Neurol.. 56・1508 (1999)