A clinical and genetic study on early-onset Alzheimer's disease associated with presenilin-1 in three Chinese families
10.3760/cma.j.issn.0254-9026.2021.06.008
- VernacularTitle: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
- Author:
Sujie LU
1
;
Yuanyan GAO
;
Chenxi XU
;
Huidong TANG
;
Li CAO
Author Information
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
- Keywords:
Alzheimer disease;
Presenilin-1;
Genetics
- From:
Chinese Journal of Geriatrics
2021;40(6):727-732
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and genetic features of early-onset Alzheimer's disease(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 were analyzed and summarized.Peripheral blood of three probands and their relatives was collected and the genes were detected by second generation sequencing(Next Generation Sequencing, NGS). Pathogenic mutations carried by the probands were identified by whole exome sequencing and then verified by Sanger sequencing in the probands and their families.Furthermore, the clinical and genetic characteristics of EOAD were discussed.Results:The first case was familial EOAD, with the heterozygous mutation c. 851C>T(p.P284L)in exon 8 of PSEN1.The second was also a case of familial EOAD, involving the heterozygous deletion mutation c. 497_499del(p.Ile167del)in exon 6 of PSEN1.In the third proband, there was no family history and the c. 626G>A(G209E)mutation was found 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 and bowel incontinence, psychiatric and other symptoms.Conclusions:These mutations represent additional mutation types and clinical manifestations in EOAD patients.Examining the genetic characteristics of PSEN1 in EOAD may contribute to the understanding of the pathogenesis, genetic classification and clinical diagnosis of EOAD.
