家族性帕金森病相关遗传基因LRRK2的差异性研究  

Differential study on familial Parkinson's disease in interrelated gene LRRK2

作　　者：姜立刚[1] 李海平[1] 王朝辉[1] 孙博谦[1] 李威[1] 

机构地区：[1]北华大学附属医院神经内科,吉林吉林132000

出　　处：《中风与神经疾病杂志》2015年第5期411-414,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的研究汉族人群家族性帕金森病的LRRK2基因的突变情况,并考察其存在的遗传差异性。方法收集21例家族性帕金森病患者,其中有3例来源于同一家族。采集外周血,提取基因组DNA作为模板,扩增LRRK2基因上的p.K616R、p.R1441G、p.R1441C、p.Y1699C、p.G2019S、p.I2020T及p.G2385R 7种突变位点的目标区域,扩增产物经电泳验证后进行Sanger测序,分析LRRK2基因的7种突变类型在样本中的分布情况。采用123I-IMP SPECT分析来自同一家族的3例帕金森病患者的脑缺血情况。结果 Sanger测序结果显示,p.G2385R突变型有5例(23.8%),p.R1441G突变型有3例(14.3%),p.K616R突变型有2例(4.76%),而其他突变型如p.G2019S、p.R1441C、p.Y1699C及p.I2020T则未检出(0%)。123I-IMP SPECT结果显示,对于来源于同一家族的3例帕金森病患者,患者2d的123I123I-IMP SPECT结果未见异常;患者1h的123I-IMP SPECT结果则显示患者双侧额叶区血流量明显下降;患者2b的123I-IMP SPECT结果则显示患者右侧基底节区血流量明显下降。结论首次在中国人群中发现来自一个家族的3例携带p.R1441G突变基因的帕金森患者,其他基因突变型的分布频率也与以往其他地区和种族的研究结果存在明显差异,证实家族性帕金森病携带的LRRK2基因突变型及突变频率均存在区域和种族的差异性。携带p.R1441G突变基因的帕金森患者与先天性帕金森病特征存在差异,原因尚不明确。Objective To research the mutations of LRRK2 gene and the genetic differences in familial Parkinson＇ s disease in Han population. Method We studied 21 familial PD patients from Han population, genomic DNA from each subject was extracted from peripheral blood. Target regions of LRRK2 gene that have been frequently reported to contain PD-associated mutations （ p. K616R, p. R1441G, p. R1441C, p. Y1699C, p. G2019S, p. I2020T and G2385R） were ana- lyzed by polymerase chain reaction-direct sequencing, mira I-IMP SPECT was used for analyzing the change of eerebral blood flow of three patients from the same family. Result Sanger sequencing results showed that 5 cases p. G2385R mu- tant （23.8%） ,3 cases p. R1441G mutant （14.3%） ,2 cases p. K616R mutant （4.76%） ,0 case p. G2019S,p. R1441C, p. Y1699C and p. I2020T （0%）. 123I-IMP SPECT results from the 3 cases of patients （2d,lh and 2b） from the same fam- ily showed that the result from patient 2d is normal,the bilateral frontal region blood flow from patient lh decreased signifi- cantly, and the right basal ganglia blood flow from patient 2b decreased significantly. Conclusion The p. R1441G mutant is found from a family of 3 patients, p. G2385R mutant is most common. Compared with the other regions and races of the world ,the frequency of LRRK2 gene mutations exists obvious difference. The feature of PD patients carrying the p. R1441G mutant has difference with the congenital Parkinson＇ disease, but the result is not clear.

关 键 词：家族性帕金森病 LRRK2基因 基因突变 Sanger测序 

分 类 号：R742.5[医药卫生—神经病学与精神病学]