Li Yu-Sheng, Yang Zhi-Hua, Zhang Yao, Yang Jing, Shang Dan-Dan, Zhang Shu-Yu, Wu Jun, Ji Yan, Zhao Lu, Shi Chang-He, Xu Yu-Ming
1Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China.
2Department of Neurology, Luoyang Central Hospital affiliated to Zhengzhou University, Henan, China.
Aging Dis. 2019 Aug 1;10(4):908-914. doi: 10.14336/AD.2018.1109. eCollection 2019 Aug.
Presenilin 1 (), presenilin 2 (), and amyloid precursor protein () mutations are responsible for autosomal dominant early-onset Alzheimer's disease (AD-EOAD). To analyze the phenotypes and genotypes of EOAD patients, we performed comprehensive clinical assessments as well as mutation screening of , , and exons 16 and 17 of by Sanger sequencing in the three Chinese EOAD families. We identified two novel mutations of (Y256N and H214R) in samples from these families, and a mutation of (G206V) in a patient with very early-onset sporadic Alzheimer's disease. A combination of bioinformatics tools based on evolutionary, structural and computational methods predicted that the mutations were all deleterious. These findings suggest that Y256N, H214R, and G206V need to be considered as potential causative mutations in EOAD patients. Further functional studies are needed to evaluate the roles of these mutations in the pathogenesis of AD.
早老素1（PS1）、早老素2（PS2）和淀粉样前体蛋白（APP）突变是常染色体显性早发性阿尔茨海默病（AD-EOAD）的病因。为分析早发性阿尔茨海默病（EOAD）患者的表型和基因型，我们对三个中国EOAD家系进行了全面的临床评估，并通过桑格测序对PS1、PS2以及APP的第16和17外显子进行了突变筛查。我们在这些家系的样本中鉴定出PS1的两个新突变（Y256N和H214R），以及一名极早发性散发性阿尔茨海默病患者的APP突变（G206V）。基于进化、结构和计算方法的生物信息学工具组合预测这些突变均具有有害性。这些发现表明，PS1的Y256N、H214R以及APP的G206V应被视为EOAD患者潜在的致病突变。需要进一步开展功能研究以评估这些突变在阿尔茨海默病发病机制中的作用。
