Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Curr Alzheimer Res. 2019;16(8):764-769. doi: 10.2174/1567205016666190806161342.
The rate of occurrence of Alzheimer's disease is increasing around the world. However, there is still no significant breakthrough in the study of its etiology and pathogenesis.
To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer software.
Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing were performed in the proband. Mutation sites were verified in 158 subjects.
We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected family members, 50 sporadic Alzheimer's disease patients and 100 control subjects.
A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer's disease has been reported, besides， it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer's disease.
全球范围内阿尔茨海默病的发病率正在不断增加。然而，在其病因和发病机制的研究方面仍未有重大突破。
筛选阿尔茨海默病的致病基因，可能有助于阐明阿尔茨海默病的发病机制，并通过各种计算机软件预测其致病性。
对先证者进行临床和神经影像学检查、全外显子组测序和 Sanger 测序。在 158 名受试者中验证了突变位点。
我们报道了一例携带可能为新发病理性突变的先证者，其临床表现为进行性记忆丧失、视空间障碍、失用症、精神行为障碍、气质和人格改变。全外显子组测序在第 5 外显子的密码子 222 （Q222L）检测到一个新的错义突变，这是一个杂合的 A 到 T 点突变，位置在 665（c.665A>T），导致谷氨酰胺到亮氨酸取代。该突变也通过 Sanger 测序在一个家族成员中得到确认；然而，在其他 7 个未受影响的家族成员、50 名散发性阿尔茨海默病患者和 100 名对照中未检测到该突变。
在中国一个早发性阿尔茨海默病家系中发现了早发性阿尔茨海默病的 1 号前蛋白基因（PSEN1）外显子 5 中一个新的突变（Gln222Leu），此外，该错义突变可能是一种新的致病性突变，这是在中国一个早发性阿尔茨海默病家系中首次报道。
