早发性帕金森综合征的PINK1基因变异分析(英文)  

Mutation analysis of PINK1 gene in patients with early-onset Parkinsonism

作　　者：张学伟[1] 张海南[2] 廖冰[1] 郭纪锋[1] 夏昆[3] 唐北沙[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]中南大学湘雅二医院神经内科,长沙410011 [3]中南大学医学遗传学国家重点实验室,长沙410008

出　　处：《中南大学学报（医学版）》2011年第6期490-497,共8页Journal of Central South University ：Medical Science

基　　金：supported by the Major State Basic Research Development Program of China(“973” Program)(2006cb500700);the National High-tech R&D Program of China(“863” Program)(2006AA02A408);the National Natural Science Foundation of China(30770735,30971035,30900469)

摘　　要：目的:探讨中国大陆汉族早发性帕金森综合征(early-onset Park inson ism,EOP)患者PTEN诱导激酶1(PTEN-induced k inase 1,PINK1)基因突变特点。方法:在149例汉族EOP患者中应用DNA直接测序技术(DNA sequenc ing)检测PINK1基因点突变及小的插入/缺失,应用实时荧光定量PCR(quantitative real-tim e polym erase chain reaction,qRT-PCR)技术检测PINK1基因大片段插入/缺失及重排突变。结果:在本组EOP患者中共发现5例患者存在4个突变,包括3个点突变c.832C>G,c.938C>T和c.1 220G>A,1个第3～8号外显子杂合缺失,其中c.832C>G为新突变;14个已知多态位点,1个新多态位点c.899+18G>A。对多态位点c.189C>T的卡方检验显示EOP组与正常对照组差异有统计学意义(基因型χ2=21.244,P<0.0001;T等位基因χ2=24.353,P<0.0001),对多态位点c.960-5G(A的卡方检验显示EOP组与正常对照组差异有统计学意义(基因型χ2=6.524,P=0.038;A等位基因χ2=6.725,P=0.0095)。结论:中国大陆汉族EOP患者中存在PINK1基因点突变以及外显子重排突变,本组EOP患者PINK1基因突变率为3.35%,多态位点c.189C>T与c.960-5G>A为中国大陆EOP患者易感因素。Objective To determine the frequency of mutations in PINK1 in Chinese Han people with sporadic early-onset Parkinsonism（EOP）.Methods DNA sequencing was used to detect point mutations and small deletions/insertions,and quantitative real-time PCR was carried out to detect deletions/insertions and rearrangements in 149 patients and 150 healthy controls.Results Four heterozygous mutations in PINK1 were identified,including 3 missense mutations（c.832CG,c.938CT,c.1 220GA） and ex 3-8 del.A novel single nucleotide polymorphism（SNP） c.899＋18GA and 14 reported SNPs were identified.Chi-square test showed that c.189C T and c.960-5G﹥A had significant difference in the genotype frequencies and allele frequencies between the patients and the controls（for c.189CT genotype χ2=21.244,P0.0001;T allele χ2=24.353,P0.0001,and for c.960-5G﹥A genotype＇s χ2=6.524,P =0.038;A allele χ2=6.725,P=0.0095）.Conclusion About 3.35% Chinese Han patients with EOP carry mutations in PINK1.Two SNPs c.189CT and c.960-5GA may contribute to the risk of EOP in Chinese Han people.

关 键 词：早发性帕金森综合征 PINK1 突变 DNA直接测序 实时荧光定量PCR 

分 类 号：R742.5[医药卫生—神经病学与精神病学]