N'Songo Aurelie, Carrasquillo Minerva M, Wang Xue, Nguyen Thuy, Asmann Yan, Younkin Steven G, Allen Mariet, Duara Ranjan, Custo Maria T Greig, Graff-Radford Neill, Ertekin-Taner Nilüfer
Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Department of Health Science Research, Mayo Clinic, Jacksonville, FL, USA.
J Alzheimers Dis. 2017;56(4):1215-1222. doi: 10.3233/JAD-161185.
We conducted a comprehensive screening of rare coding variants in an African American cohort to identify novel pathogenic mutations within the early-onset Alzheimer's disease (EOAD) genes (APP, PSEN1, and PSEN2) in this understudied population. Whole-exome sequencing of 238 African American subjects identified 6 rare missense variants within the EOAD genes, which were observed in AD cases but never among controls. These variants were analyzed in an independent cohort of 300 African American subjects in which PSEN2:NM_000447:exon5:c.T331C:p.Phe111Leu and PSEN1-minilin rs777923890 variants were again not observed, indicating that these novel rare variants, may contribute to AD risk in this population.
我们对一个非裔美国人队列进行了罕见编码变异的全面筛查，以在这个研究较少的人群中确定早发性阿尔茨海默病（EOAD）基因（APP、PSEN1和PSEN2）内的新型致病突变。对238名非裔美国人受试者进行全外显子组测序，在EOAD基因中鉴定出6个罕见错义变异，这些变异在AD病例中观察到，但在对照中从未出现过。在一个由300名非裔美国人组成的独立队列中对这些变异进行了分析，其中再次未观察到PSEN2:NM_000447:exon5:c.T331C:p.Phe111Leu和PSEN1-小菌素rs777923890变异，表明这些新型罕见变异可能导致该人群患AD的风险。
