Analysis of α-synuclein, parkin, tau, and UCH-L1 in a Japanese family fo autosomal dominant Parkinsonism

常染色体显性帕金森病日本家系的 α-突触核蛋白、parkin、tau 和 UCH-L1 分析

• 批准号: 10670600
• 负责人: HASEGAWA Kazuko
• 金额: $ 0.58万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670600/
• 关键词: family parkinsonism; etiology; mutation; 家族性パーキンソン病; 遺伝子; 常染色体優性遺伝

Objectives-----To examine whether autosomal dominant parkinsonism of a Japanese family, Sagamihara family, was due to the mutations of α-synuclein, parkin, tau, and UCH-L1, which have been reported as the causal genes for parkinsonism in other families.Methods-----Point mutations ofα-synuclein exons 3 and 4 were investigated by digesting polymerase-chain reaction (PCR) amplified genomic DNA fragments. Exon deletion of parkin was examined by amplifying exons 3, 4, 5, 6 and 7 by PCR. Point mutations of tau exons 9, 10, 12, and 13 and intron 10, and of UCH-L1 exon 4 were analyzed by direct sequencing of the PCR-amplified DNA fragments of each exon and intron.Results-----No point mutation was detected inα-synuclein exon 3 or 4. No exon deletion was detected in parkin exon 3, 4, 5, 6 or 7. The sequences of tau exons 9, 10, 12 and 13 as well as intron 10 were normal. The UCH-L1 sequence of exon 4 through the beginning of intron 4 was also normal including a polymorphic nucleotide substitution.Conclusion-----The parkinsonism of the Sagamihara family seems not to be due to previously identified point mutations of α-synuclein, tau, or UCH-L1, or to exon deletion of parkin.

目的探讨日本相模原家族的常染色体显性遗传性帕金森病是否与α-synuclein、parkin、tau和UCH-L1基因突变有关。PCR扩增parkin基因第3、4、5、6、7外显子，检测其缺失情况。对tau蛋白外显子9、10、12、13和内含子10以及UCH-L1外显子4进行点突变分析。在parkin外显子3、4、5、6和7中未检测到外显子缺失。tau蛋白外显子9、10、12和13以及内含子10的序列正常。UCH-L1基因第4外显子至第4内含子起始部分的序列也是正常的，包括一个多态性的核苷酸替换。结论--相模原家族的帕金森综合征似乎不是由于先前发现的α-突触核蛋白、tau蛋白或UCH-L1的点突变，也不是由于parkin基因外显子缺失。

项目成果

K.HASEGAWA: "Autosomal dominant Parkinsonism"Prog. Med.. 180. 99-102 (1998)

K.HASEGAWA：“常染色体显性帕金森病”Prog。

長谷川一子: "家族性パーキンソニズム"pvcgress in Medicrie. 19. 66-71 (1999)

长谷川和子：Medicrie 中的“家族性帕金森症”pvcgress。19. 66-71 (1999)

長谷川一子: "パーキンソン病の臨床微候・診断基準"カレントテラビー. 17. 1165-1170 (1999)

长谷川和子：“帕金森病的临床症状和诊断标准”《当代电视》17. 1165-1170 (1999)。

長谷川一子: "パーキンソン病の臨床徴候 診断基準"カレントテラピー. 17. 1165-1170 (1999)

Kazuko Hasekawa：“帕金森病的临床症状和诊断标准”《当前疗法》17. 1165-1170 (1999)。

長谷川一子: "進行性淡蒼球変性症"日本臨床. 27. 74-77 (1999)

长谷川和子：“进行性苍白球变性”日本临床杂志 27. 74-77 (1999)。