早老素1基因突变伴晚发型阿尔茨海默病家系基因与影像学分析

Analysis of gene and imaging on a late onset Alzheimer's pedigree concomitant with presenilin 1 mutation

目的分析早老素1基因突变伴晚发型阿尔茨海默病(Alzheimer's disease,AD)家系的临床表现、影像资料及基因突变。方法临床收集并分析该家系中患者的临床表现及相关检查结果,采集先证者及其儿子的血样,采用二代测序方法进行家族性AD相关基因的筛查,并对突变位点进行一代测序验证。结果家系中3名成员具有AD表现,其中2名为晚发型AD。先证者核磁共振影像呈现多发脑叶微出血,其早老素1基因8号外显子编码区第865号核苷酸由T变为C,导致第289号氨基酸由Ser变为Pro(p.Ser289Pro),为错义突变。结论早老素1基因发生p.S289P突变可能会导致晚发型家族性AD,且伴淀粉样血管病表现。

Objective To analyze the clinical manifestation, imaging data and genetics mutation variants of late onset familial Alzheimer's disease concomitant with a novel mutation of presenilin 1. Methods The clinical manifestations and auxiliary examination recordings of the pedigree were analyzed.DNA was extracted from peripheral blood samples of the proband and her sons.Mutational analysis was performed by the next-generation sequencing technology and the mutation event was confirmed by Sanger sequencing technology. Results Two patients of the family presenting as Alzheimer's dementia were late onset.MRI of the proband showed extensive cerebral microbleeds.The gene detection showed p. S289P mutation in the exon 8 of presenilin 1 of the proband. Conclusion Mutation of p. S289P in the presenilin 1 gene may contribute to late onset Alzheimer's disease accompanied by amyloid angiopathy.