title: Detecting gene mutations in Japanese Alzheimer's patients by semiconductor sequencing.
abstract: Alzheimer's disease (AD) is the most common form of dementia. To date, several genes have been identified as the cause of AD, including PSEN1, PSEN2, and APP. The association between APOE and late-onset AD has also been reported. We here used a bench top next-generation sequencer, which uses an integrated semiconductor device, detects hydrogen ions, and operates at a high-speed using nonoptical technology. We examined 45 Japanese AD patients with positive family histories, and 29 sporadic patients with early onset (<60-year-old). Causative mutations were detected in 5 patients in the familial group (11%). Three patients had a known heterozygous missense mutation in the PSEN1 gene (p.H163R). Two patients from 1 family had a novel heterozygous missense mutation in the PSEN1 gene (p.F386L). In the early onset group, 1 patient carrying homozygous APOEε4 had a novel heterozygous missense mutation in the PSEN2 gene (p.T421M). Approximately 43% patients were APOEε4 positive in our study. This new sequencing technology is useful for detecting genetic variations in familial AD.
authors.affiliation: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Yagi
authors.affiliation: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan; Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Miyamoto
authors.affiliation: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morino
authors.affiliation: Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima, Japan.
authors.forename: Yuishin
authors.initials: Y
authors.lastname: Izumi
authors.affiliation: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Kuramochi
authors.affiliation: Department of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kurashige
authors.affiliation: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Mizuno
authors.affiliation: Department of Periodontal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan. Electronic address: hkawakam@hiroshima-u.ac.jp.
authors.forename: Hideshi
authors.initials: H
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D044466:Asian People; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D053764:Presenilin-1 / Q000235:genetics*; D053766:Presenilin-2 / Q000235:genetics*; D011522:Protons; D012666:Semiconductors; D017422:Sequence Analysis, DNA / Q000295:instrumentation* / Q000379:methods
chemical_list: D053327:Apolipoprotein E4; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D011522:Protons
keywords: APOE; Alzheimer's disease; Ion sequencing technology; Mutations; PSEN1; PSEN2