title: Identification of PSEN1 mutations p.M233L and p.R352C in Han Chinese families with early-onset familial Alzheimer's disease.
abstract: Early-onset familial Alzheimer's disease (EOFAD) is characterized by the onset of dementia symptoms before 65 years, positive family history, high genetic predisposition, and an autosomal dominant inheritance. We aimed to investigate mutations and to characterize phenotypes in Chinese EOFAD families. Detailed clinical assessments and genetic screening for mutations in the presenilin 1 (PSEN1), presenilin 2, amyloid precursor protein, and APOE genes were carried out in 4 EOFAD families. Two PSEN1 mutations (p.R352C and p.M233L) were identified in 2 EOFAD families, respectively. Mutation p.M233L was associated with prominent very early onset, rapidly progressive dementia, and neurologic symptoms, whereas p.R352C was associated with a progressive dementia, psychiatric syndrome, and chronic disease course. Both mutations are predicted to be pathogenic. Our results showed that mutations in PSEN1 gene might be common in Chinese EOFAD families.
authors.affiliation: Laboratory for Conservation and Utilization of Bioresource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China; Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, P.R. China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Li
authors.affiliation: Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, P.R. China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Shao-Xing
authors.initials: SX
authors.lastname: Dai
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bi
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, P.R. China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.affiliation: Department of Radiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Zong-Fang
authors.initials: ZF
authors.lastname: Li
authors.affiliation: Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Laboratory for Conservation and Utilization of Bioresource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Tai-Cheng
authors.initials: TC
authors.lastname: Zhou
authors.affiliation: Laboratory for Conservation and Utilization of Bioresource & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming, Yunnan, China. Electronic address: yuli-1220@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China; Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, P.R. China; CAS Center for Excellence in Brain Science, Chinese Academy of Sciences, Shanghai, 200031, China. Electronic address: yaoyg@mail.kiz.ac.cn.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D002648:Child; D003704:Dementia / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D053764:Presenilin-1 / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2
keywords: Chinese; Early-onset familial Alzheimer's disease; Mutation; PSEN1