与Presenilin-1相关的早发型阿尔茨海默病家系临床及遗传学研究  

A clinical and genetic study on early-onset Alzheimer's disease associated with presenilin-1 in three Chinese families

作　　者：陆素洁 高媛妍 徐晨曦 汤荟冬[2] 曹立[2] Lu Sujie;Gao Yuanyan;Xu Chenxi;Tang Huidong;Cao Li(Department of Neurology,Civil Aviation Shanghai Hospital Gubei Branch,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200336,China;Department of Neurology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai200025,China)

机构地区：[1]民航上海医院上海交通大学医学院附属瑞金医院古北分院神经内科,200336 [2]上海交通大学医学院附属瑞金医院神经内科,200025

出　　处：《中华老年医学杂志》2021年第6期727-732,共6页Chinese Journal of Geriatrics

摘　　要：目的探讨早发型阿尔茨海默病(EOAD)先证者及其家系的临床与遗传学特点和致病基因突变特征。方法︰对3例EOAD先证者及其家庭成员进行分析并总结临床特点。对3例先证者及其亲属采集外周血,运用二代测序(NGS)方法进行基因检测,通过外显子捕获测序发现先证者携带的致病突变,进一步通过Sanger测序对先证者及其家属的该基因位点进行验证。进一步探讨EOAD的临床及遗传学特点。结果第一例为家族性EOAD,基因突变类型为presenilin-1(PSEN1)基因8号外显子存在的c.851C>T(p.P284L)杂合突变。第二例也为家族性EOAD,基因突变类型为PSEN1基因第6号外显子的c.497_499del(p.Ile167del)杂合缺失突变。第三例先证者无家族史,受检者样本中发现PSEN1基因7号外显子上存在c.C626C>A(G209E)杂合突变。3例患者均以记忆力下降为首发症状,伴随的临床表现有行动迟缓、步态异常、言语不清、大小便失禁﹑精神症状等。结论﹑丰富了EOAD患者的突变类型及EOAD患者的临床表现,总结该基因与EOAD的遗传学特点可以增加对该病发病机制的认知,并为遗传分类和临床诊断提供帮助。ObjectiveTo investigate the clinical and genetic features of early-onset Alzheimersdisease(EOAD)and the characteristics of pathogenic mutations in probands and their families.Methods Clinical and genetic features of three EOAD probands and their family members China wereanalyzed and summarized.Peripheral blood of three probands and their relatives was collected and thegenes were detected by second generation sequencing(Next Generation Sequencing,NGS).Pathogenicmutations carried by the probands were identified by whole exome sequencing and then verified bySanger sequencing in the probands and their families.Furthermore,the clinical and geneticcharacteristics of EOAD were discussed.Results The first case was familial EOAD,with theheterozygous mutation c.851C>T(p.P284L)in exon 8 of PSEN1.The second was also a case offamilial EOAD,involving the heterozygous deletion mutation c.497_499del(p.Ile167del)in exon 6 ofPSEN1.In the third proband,there was no family history and the c.626G>A(G209E)mutation wasfound in exon 7 of the PSEN1 gene.All three patients had memory loss as their first symptom,accompanied by clinical manifestations of slow movement,abnormal gait,unclear speech,bladder andbowel incontinence,psychiatric and other symptoms.Conclusions These mutations representadditional mutation types and clinical manifestations in EOAD patients.Examining the geneticcharacteristics of PSEN1 in EOAD may contribute to the understanding of the pathogenesis,geneticclassification and clinical diagnosis of EOAD.

关 键 词：阿尔茨海默病 PRESENILIN-1 遗传学 

分 类 号：R749.16[医药卫生—神经病学与精神病学]