摘要
目的:探讨遗传因素对良性特发性眼睑痉挛(BEB)的可能影响。方法:选择2015年4月至2015年10月在武汉大学人民医院神经内科运动障碍专病门诊就诊的BEB患者20例。采取问卷调查的方式详细调查患者的情况,调查内容包括一般情况、病史摘要、治疗情况、既往病史(高血压病、糖尿病、脑外伤等)、家族史、危险/保护因素调查(吸烟、饮酒、饮茶、咖啡等)。在患者知情同意的情况下,抽取患者静脉血3-5ml。采用二代测序方法,检测可能导致运动障碍临床表现各类疾病相关的基因共151种,包括肌张力障碍27种、发作性共济失调4种、发作性运动诱发性运动障碍2种、发作性非运动诱发性运动障碍1种、特发性震颤3种、帕金森病78种以及ADCK3、AFG3L2、ANO10等。结果:20例患者中,男3例、女17例,平均年龄55.25(31-72)岁,病程平均6.15(1-24)年;有家族史者2例。未发现任何一种基因突变者2例;检测出两种基因突变者7例;SYNE1基因突变7例,CIZ1基因突变2例,CACNA1A基因突变2例,LRRK2基因突变2例,FUS基因突变2例;C10orf2、TPP1、SLC1A3、PNKD、EIF4G1、SETX、PRRT2、SPTBN2和TTBK2基因突变者各1例。结论:眼睑痉挛和其它肌张力障碍性疾病一样,存在遗传学基础。CIZ1和SYNE1基因突变极有可能与眼睑痉挛有关。我们需要扩大样本量来进一步筛选基因,或通过家系研究来寻找易感基因。并进一步在动物实验中验证。
Objective:To explore the impact of genetic factors to the etiology of benign essential blepharospasm(BEB).Methods:There were 20 BEB patients between April,2015 and October,2015,who were diagnosed by clinical manifestations.All the cases were investigated by questionnaires about general conditions,physical examination,treatment,medical history(hypertension,diabetes,brain trauma,etc),family history,risk/protective factors survey(smoking,drinking,tea,coffee,etc).In the case of patients with informed consent,we detected 151 genes that lead to movement disorders through second-generation sequencing methods,including 27 genes related to dystonia,4genes related to episodic ataxia,2genes related to paroxysmal kinesigenit dyskinesia,1gene related to paroxysmal non-kinesigenic dyskinesia,3genes related to essential tremor,78 genes related to Parkinson's disease and ADCK3,AFG3L2,ANO10 and so on.Results:Two patients in 20 cases of blepharospasm had a family history.We found SYNE1 mutation in seven ca-ses,CIZ1 mutation in two cases,CACNA1 A mutation in two cases,two cases of LRRK2 mutations,two cases of FUS mutations,and only 1 patient had mutations in C10orf2,TPP1,SLC1A3,PNKD,EIF4G1,SETX,PRRT2,SPTBN2,TTBK2,separately.Two patients did not showed any mutations of these 151 genes.Some patients were detected two mutations.Conclusion:Similar to other dystonia diseases,the genetic factors may contribute to the etiology of blepharospasm.There may be a close relationship between CIZ1/SYNE1 mutations and blepharospasm.We need to expand the sample size for further screening genes or familial studies to find susceptibility genes,and carry out further validation in animal experiments.
出处
《武汉大学学报（医学版）》
CAS
2017年第3期459-466,共8页
Medical Journal of Wuhan University
基金
湖北省卫计委重点项目(编号:WJ2015MA007)
关键词
良性特发性眼睑痉挛
遗传
二代测序
基因突变
Benign Essential Blepharospasm
Genetic
Second-Generation Sequencing
Gene Mutation
