Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China.
Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China.
复制标题
中国阿尔茨海默病、肌萎缩侧索硬化症和额颞叶痴呆患者 CHCHD2 突变的鉴定。
DOI：
10.3892/mmr.2018.8962
复制
发表时间：
2018
影响因子：
3.4
通讯作者：
Lu Shen
中科院分区：
文献类型：
--
作者：
Xi;Bin Jiao;Weiwei Zhang;Tingting Xiao;Li;Chuzheng Pan;B. Tang;Lu Shen
最近，卷曲螺旋结构域 2 (CHCHD2) 基因被确定为帕金森病 (PD) 的可能致病基因。另外三种神经退行性疾病，阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTD），在临床表型、病理特征和遗传遗传上与PD有显着重叠，目前尚不清楚CHCHD2变异是否可以解释这三种疾病。本研究筛查了来自中国汉族人群的总共 780 名患者（511 名 AD、181 名 ALS 和 88 名 FTD）和 500 名健康对照者的 CHCHD2 基因的所有外显子。在五名不相关的 AD 患者中发现了两种错义变异，5C>T (Pro2Leu) 和 238A>G (Ile80Val)，而在 ALS 或 FTD 患者中未观察到突变。这些突变在 ExAC 数据库中被报告为低频变异，频率为 0.0075 和 0.000025。然而，Pro2 Leu 在对照组中也被检测到，并被证实与 AD 风险没有显着关联；在任何正常对照中均未检测到 Ile80Val，这表明 CHCHD2 基因可能与中国汉族人群中的 AD 相关。
Recently, the coiled‑coil‑helix‑coiled‑coil‑helix domain 2 (CHCHD2) gene was identified as a possible causative gene for Parkinson's disease (PD). Three other neurodegenerative diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), share significant overlaps with PD in clinical phenotypes, pathological features and genetic heredities, and it is still unclear whether CHCHD2 variants could explain these three diseases. The present study screened all exons of the CHCHD2 gene in a total of 780 patients (511 AD, 181 ALS and 88 FTD) and 500 healthy controls from the Chinese Han population. Two missense variants, 5C>T (Pro2Leu) and 238A>G (Ile80Val), were identified in five unrelated patients with AD while no mutations were observed in patients with ALS or FTD. These mutations have been reported as low‑frequency variants in the ExAC database with frequencies of 0.0075 and 0.000025. Pro2 Leu, however, was also detected in controls and was confirmed to have no significant association with the risk for AD; Ile80Val was not detected in any normal controls, suggesting that the CHCHD2 gene may be associated with AD in the Chinese Han population.