eprintid: 1431635 rev_number: 34 eprint_status: archive userid: 608 dir: disk0/01/43/16/35 datestamp: 2014-06-06 19:21:47 lastmod: 2021-09-19 23:34:40 status_changed: 2014-06-06 19:21:47 type: article metadata_visibility: show item_issues_count: 0 creators_name: Sassi, C creators_name: Guerreiro, R creators_name: Gibbs, R creators_name: Ding, J creators_name: Lupton, MK creators_name: Troakes, C creators_name: Lunnon, K creators_name: Al-Sarraj, S creators_name: Brown, KS creators_name: Medway, C creators_name: Lord, J creators_name: Turton, J creators_name: Mann, D creators_name: Snowden, J creators_name: Neary, D creators_name: Harris, J creators_name: Bras, J creators_name: ARUK Consortium, - creators_name: Morgan, K creators_name: Powell, JF creators_name: Singleton, A creators_name: Hardy, J title: Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: APP, British cohort, Early-onset Alzheimer's disease, PSEN1, PSEN2 note: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). Copyright © 2014 The Authors. Published by Elsevier Inc. abstract: Early-onset Alzheimer's disease (EOAD) represents 1%-2% of the Alzheimer's disease (AD) cases, and it is generally characterized by a positive family history and a rapidly progressive symptomatology. Rare coding and fully penetrant variants in amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are the only causative mutations reported for autosomal dominant AD. Thus, in this study we used exome sequencing data to rapidly screen rare coding variability in APP, PSEN1, and PSEN2, in a British cohort composed of 47 unrelated EOAD cases and 179 elderly controls, neuropathologically proven. We report 2 novel and likely pathogenic variants in PSEN1 (p.L166V and p.S230R). A comprehensive catalog of rare pathogenic variants in the AD Mendelian genes is pivotal for a premortem diagnosis of autosomal dominant EOAD and for the differential diagnosis with other early onset dementias such as frontotemporal dementia (FTD) and Creutzfeldt-Jakob disease (CJD). date: 2014-05-02 official_url: http://dx.doi.org/10.1016/j.neurobiolaging.2014.04.026 vfaculties: VFBRS oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: JOURNAL ARTICLE verified: verified_manual elements_source: PubMed elements_id: 950449 doi: 10.1016/j.neurobiolaging.2014.04.026 pii: S0197-4580(14)00328-5 lyricists_name: Hardy, John lyricists_name: Louro Guerreiro, Rita lyricists_name: Sassi, Celeste lyricists_name: Smalley, June lyricists_name: Tomas Bras, Jose lyricists_id: JHARD28 lyricists_id: RJLOU51 lyricists_id: CSASS81 lyricists_id: JASMA87 lyricists_id: JMTOM86 full_text_status: public publication: Neurobiol Aging volume: 35 number: 10 pagerange: 2422.e13-2422.e16 citation: Sassi, C; Guerreiro, R; Gibbs, R; Ding, J; Lupton, MK; Troakes, C; Lunnon, K; ... Hardy, J; + view all <#> Sassi, C; Guerreiro, R; Gibbs, R; Ding, J; Lupton, MK; Troakes, C; Lunnon, K; Al-Sarraj, S; Brown, KS; Medway, C; Lord, J; Turton, J; Mann, D; Snowden, J; Neary, D; Harris, J; Bras, J; ARUK Consortium, -; Morgan, K; Powell, JF; Singleton, A; Hardy, J; - view fewer <#> (2014) Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease. Neurobiol Aging , 35 (10) 2422.e13-2422.e16. 10.1016/j.neurobiolaging.2014.04.026 <https://doi.org/10.1016/j.neurobiolaging.2014.04.026>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1431635/1/1-s2.0-S0197458014003285-main.pdf