摘要目的 探讨中国人早发型家族性阿尔茨海默病早老素1基因(presenilin 1,PSEN1的突变情况.方法 对1个早发型家族性阿尔茨海默病家系中的17名成员(包括5例患者)、10例散发型阿尔茨海默病患者和100名家系外非患病个体的PSEN1的第1～13外显子进行测序.结果 该家系中的6位成员PSEN1第11外显子1133位点G→A突变(Gly378Glu),其中5位已发病,1位成员基因突变未达发病阶段.散发型阿尔茨海默病、家族中超过发病年龄的正常人均未发现同样的突变.结论 PSEN1基因突变可能与早发性家族性阿尔茨海默病有关,而该基因第11外显子的1133位点G→A突变(Gly378Glu)是中国人家族性阿尔茨海默病的1个新的突变位点.

abstractsObjective Mutations of presenilin 1 (PSEN1)gene are the most frequent cause for familial Alzheimer's disease (AD).This study was set to explore potential mutation of PSEN1 gene in a Chinese family featuring early-onset Alzheimer's disease (FAD).Methods DNA was isolated from peripheral blood samples from 17 members of the FAD family as well as 10 patients with sporadic Alzheimer's disease and 100 healthy subjects.With polymerase chain reaction (PCR) and Sanger sequencing,exons 1-13 of the PSEN1 gene were analyzed.Results DNA sequencing has revealed a heterozygous point mutation from G to A at position 1133 (Gly378Glu) of exon 11 ofPSEN1 gene in 6 members from the family,among whom 5 were patients with dementia,whilst the remaining 1 was clinically normal but under onset age.The same mutation was not found in all other patients and the normal controls.Conclusion A novel missense mutation of the PSEN1 gene,Gly378Glu,probably underlies the autosomal dominant early onset FAD in this Chinese family.