TY - JOUR
T1 - Evaluating pathogenic dementia variants in posterior cortical atrophy
AU - Carrasquillo, Minerva M.
AU - Barber, Imelda
AU - Lincoln, Sarah J.
AU - Murray, Melissa E.
AU - Camsari, Gamze Balci
AU - Khan, Qurat ul Ain
AU - Nguyen, Thuy
AU - Ma, Li
AU - Bisceglio, Gina D.
AU - Crook, Julia E.
AU - Younkin, Steven G.
AU - Dickson, Dennis W.
AU - Boeve, Bradley F.
AU - Graff-Radford, Neill R.
AU - Morgan, Kevin
AU - Ertekin-Taner, Nilüfer
N1 - Publisher Copyright:
© 2016 Elsevier Inc. All rights reserved.
PY - 2016
Y1 - 2016
N2 - Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against w4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE e4 association, and demonstrate the utility of NeuroX.
AB - Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology. Case studies detected mutations in PSEN1, PSEN2, GRN, MAPT, and PRNP in subjects with clinical PCA. To detect the frequency and spectrum of mutations in known dementia genes in PCA, we screened 124 European-American subjects with clinical PCA (n = 67) or posterior AD neuropathology (n = 57) for variants in genes implicated in AD, frontotemporal dementia, and prion disease using NeuroX, a customized exome array. Frequencies in PCA of the variants annotated as pathogenic or potentially pathogenic were compared against w4300 European-American population controls from the NHLBI Exome Sequencing Project. We identified 2 rare variants not previously reported in PCA, TREM2 Arg47His, and PSEN2 Ser130Leu. No other pathogenic or potentially pathogenic variants were detected in the screened dementia genes. In this first systematic variant screen of a PCA cohort, we report 2 rare mutations in TREM2 and PSEN2, validate our previously reported APOE e4 association, and demonstrate the utility of NeuroX.
KW - APOE
KW - Dementia
KW - NeuroX
KW - PCA
KW - PSEN2
KW - Posterior Alzheimer's disease
KW - TREM2
UR - http://www.scopus.com/inward/record.url?scp=84957583628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84957583628&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2015.09.023
DO - 10.1016/j.neurobiolaging.2015.09.023
M3 - Article
C2 - 26507310
AN - SCOPUS:84957583628
SN - 0197-4580
VL - 37
SP - 38
EP - 44
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -