锰中毒性帕金森综合征与线粒体基因突变的关系

Relationship between manganese induced Parkinson's syndrome and mutation of chondriogene

目的探讨线粒体DNA(mtDNA)基因突变与锰中毒性帕金森综合征之间的关系,以了解其是否为锰中毒性帕金森综合征发病中的一环。方法采用聚合酶链反应(PCR)、单链构象多态性分析(SSCP)、测序方法对临床诊断为锰中毒性帕金森综合征的18例患者和40名健康对照组的mtDNA点8344、11778及12SrRNA区域所在片段进行分析。结果有15例存在mtDNA 9bp片段缺失;在锰中毒性帕金森综合征患者中发现有4例存在mtDNA8175G>A点突变、3例存在mtDNA11914G>A点突变;所有研究对象均未检测到mtDNA点8344、11778及12SrRNA区域突变。结论广西人群mtDNA 9bp缺失率较高(25.9%);mtDNA 8175G>A和mtDNA 11914G>A点突变可能为锰中毒性帕金森综合征的1个致病突变;mtDNA点8344、11778及12SrRNA区域突变可能不是锰中毒性帕金森综合征的突变热点。

Objective To investigate the relationship between manganese- induced parkinsonism and mtDNA point mutations. Methods Eighteen patients with manganese- induced parkinsonism and forty healthy controls were enrolled. PCR was used to amplify mtDNA 8344, 11778 and 12SrRNA region segments of all participants. For the PCR products, SSCP was adopted to detect mutations and the abnormal segments were sequenced. Results The mtDNA 9-- bp deletion was identified in fifteen participants. Besides, two new mtDNA point mutations were found which had never been reported in previous literature available. The first one was mtDNA point 8175 G〉A mutation which was detected in four manganese--induced parkinsonism patients; the second one was mtDNA point 11914 G〉A mutation which was found in three manganese-- induced parkinsonism patients. However, no mutations of mtDNA 8344, 11778 and 12SrRNA region were found. Conelusions The frequency of mtDNA 9--bp deletion of Guangxi people was significantly higher than the average of the country. The mtDNA point 8175 G〉 A mutation and point 11914 G~〉A mutation may be involved in the pathogenesis of manganese-- induced parkinsonism, but this should be confirmed by future study. MtDNA point 8344, 11778 and 12SrRNA region may be not a mutational hot point or region in the pathogenesis of manganese--induced parkinsonism.