title: Probable novel PSEN2 Pro123Leu mutation in a Chinese Han family of Alzheimer's disease.
abstract: We describe a probably novel mutation in exon 5 of the presenilin 2 gene (Pro123Leu) in a Chinese familial early-onset Alzheimer's disease, which clinically manifests as progressive memory loss, cognitive impairment, parkinsonism, and myoclonic jerks. Clinical and neuroimaging examination, target region capture, and high-throughput sequencing were performed in a family of 4 generations. Cerebral perfusion and glucose metabolism were evaluated using arterial spin labeling perfusion magnetic resonance imaging and (18)F-fludeoxyglucose positron emission tomography, respectively. Target region capture sequencing yielded a novel missense mutation at codon 123 (P123L) which is a heterozygous C to T point mutation at position 368 (c.368C>T) in exon 5 of the presenilin 2 leading to a proline-to-leucine substitution. The results were also identified by Sanger sequencing in 7 family members but not in the other 9 unaffected family members and 100 control subjects. This mutation is probably pathogenic and is the first of its kind reported in an early-onset familial AD associated with atypical symptom presentation.
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Mingrong
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Radiology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Junling
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Changshui
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: zangweizhou@hotmail.com.
authors.forename: Weizhou
authors.initials: W
authors.lastname: Zang
authors.affiliation: Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address: zhangjiewen9900@126.com.
authors.forename: Jiewen
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D019943:Amino Acid Substitution / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D003062:Codon / Q000235:genetics; D003952:Diagnostic Imaging; D005091:Exons / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007930:Leucine / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D053766:Presenilin-2 / Q000737:chemistry / Q000235:genetics*; D011392:Proline / Q000235:genetics*
chemical_list: D003062:Codon; C508861:PSEN2 protein, human; D053766:Presenilin-2; D011392:Proline; D007930:Leucine
keywords: ASL; Alzheimer's disease; P123L mutation; PSEN2; Positron emission tomography