TY  - JOUR
TI  - Exome sequencing identifies 2 novel presenilin 1 mutations (p.L166V and p.S230R) in British early-onset Alzheimer's disease.
AV  - public
Y1  - 2014/05/02/
VL  - 35
SP  - 2422.e13
EP  - 2422.e16
IS  - 10
N1  - 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.
N2  - 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).
ID  - discovery1431635
UR  - http://dx.doi.org/10.1016/j.neurobiolaging.2014.04.026
JF  - Neurobiol Aging
A1  - Sassi, C
A1  - Guerreiro, R
A1  - Gibbs, R
A1  - Ding, J
A1  - Lupton, MK
A1  - Troakes, C
A1  - Lunnon, K
A1  - Al-Sarraj, S
A1  - Brown, KS
A1  - Medway, C
A1  - Lord, J
A1  - Turton, J
A1  - Mann, D
A1  - Snowden, J
A1  - Neary, D
A1  - Harris, J
A1  - Bras, J
A1  - ARUK Consortium, -
A1  - Morgan, K
A1  - Powell, JF
A1  - Singleton, A
A1  - Hardy, J
KW  - APP
KW  -  British cohort
KW  -  Early-onset Alzheimer's disease
KW  -  PSEN1
KW  -  PSEN2
ER  -