中文摘要：

目的：探讨1个中国早发型家族性阿尔茨海默病家系的基因筛查方法及其突变情况。方法收集1个早发型家族性阿尔茨海默病家系，分析其临床表现及辅助检查结果，对这个家系中的8位成员、20例散发性阿尔茨海默病（ SAD）患者和50名家系外非患病个体进行血样采集，提取基因组DNA，对其PSEN1基因的第3～12外显子、PSEN2基因的第1～12外显子、淀粉样前体蛋白（ APP）基因的第16～17外显子进行测序。结果该家系中有6位成员筛查出APP基因第17外显子发生g．275339T＞C碱基突变，使编码APP的第716个密码子由ATC变为ACC，即由异亮氨酸变为苏氨酸，发生了Ile716Thr （ I716T）突变。携带该突变的6位成员，其中1例已发病，5位尚未达到发病阶段。20例SAD患者和50名家系外非患病个体经筛查均未发现该突变。结论我们在中国人群中发现了家族性阿尔茨海默病的1个突变位点，即APP基因第17外显子I716T突变，此突变很可能与该家系的发病相关。

英文摘要：

Objective To analyze the clinical presentation and explore potential mutation of pathogenic genes in a Chinese family with early-onset familial Alzheimer′s disease （ EOFAD ） .Methods The clinical features and the results of auxiliary examination were collected and analyzed .DNA was extracted from peripheral blood samples from 8 members of the EOFAD family as well as 20 patients with sporadic Alzheimer′s disease （ SAD ） and 50 healthy controls .By polymerase chain reaction and direct DNA sequencing ,mutational analysis of presenilin 1 （ exons 3 -12 ） , presenilin 2 （ exons 1 -12 ） , and amyloid precursor protein （APP） genes （exons 16 -17） was performed.Results Molecular genetic analysis revealed that 6 patients had a mutation of g.275339T 〉C in exon 17 of APP gene, which caused ATC conversion to ACC, resulted in the amino acid substitution as Ile716Thr（I716T）.Among them one was patient with dementia ,the other five were clinically normal but under onset age .The same mutation was not found in the SAD patients and healthy controls .Conclusions We reported a novel I716T mutation in exon 17 of the APP gene in a Chinese EOFAD pedigree .This mutation probably promoted the pathogenesis of EOFAD in this Chinese pedigree , eventually resulting in dementia .