Neurobiology of aging · 2015
Evaluating pathogenic dementia variants in posterior cortical atrophy.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Carrasquillo Minerva M, Barber Imelda, Lincoln Sarah J, Murray Melissa E, Camsari Gamze Balci, Khan Qurat Ul Ain, Nguyen Thuy, Ma Li, Bisceglio Gina D, Crook Julia E, Younkin Steven G, Dickson Dennis W, Boeve Bradley F, Graff-Radford Neill R, Morgan Kevin, Ertekin-Taner Nilüfer
Аннотация
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 ∼ 4300 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 ε4 association, and demonstrate the utility of NeuroX.