The OPA1 GeneMutations Are Frequent in Han Chinese Patients with Suspected Optic Neuropathy
文献类型：期刊论文
| 作者 | Zhang AM1,2; Bi R1; Yao YG[*]1,4; Hu QX1; Fan Y1; Zhang QJ3 |
| 刊名 | Mol Neurobiol
 |
| 出版日期 | 2016 |
| 卷号 | **期号:**页码:Online |
| 关键词 | Han Chinese OPA1 Pathogenicity Suspected optic neuropathy |
| 通讯作者 | yaoyg@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | While many patients with hereditary optic neuropathies are caused by mitochondrial DNA (mtDNA) mutations of Leber's hereditary opticneuropathy (LHON), a significant proportion of them does not have mtDNA mutation and is caused by mutations in genes of the nuclear genome. In this study, we investigated whether the OPA1 gene, which is a pathogenic gene for autosomal dominant optic atrophy (ADOA), is frequently mutated in these patients. We sequenced all 29 exons of the OPA1 gene in 105 Han Chinese patients with suspected LHON. mtDNA copy number was quantified in blood samples from patients with and without OPA1 mutation and compared to healthy controls. In silico program-affiliated prediction, evolutionary conservation analysis, and in vitro cellular assays were performed to show the potential pathogenicity of the mutations. We identified nine OPA1 mutations in eight patients; six of them are located in exons and three are located in splicing sites. Mutation c.1172T > G has not been reported before. When we combined our data with 193 reported Han Chinese patients with optic neuropathy and compared to the available data of 4327 East Asians by the Exome Aggregation Consortium (ExAC), we found a significant enrichment of potentially pathogenic OPA1 mutations in Chinese patients. Cellular assays for OPA1 mutants c.869G > A and c.2708_2711del showed abnormalities in OPA1 isoforms, mitochondrial morphology, and cellular reactive oxygen species (ROS) level. Our results indicated that screeningOPA1 mutation is needed for clinical diagnosis of patients with suspected optic neuropathy. |
| 收录类别 | SCI |
| 资助信息 | This study was supported by National Natural Science Foundation of China (grant number 81200725) and the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003). |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/10546]  |
| 专题 | 昆明动物研究所_重大疾病机理的遗传学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 2.Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China 3.State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China 4.CAS Center for Excellence in Brain Science and Intelligence Technology, ChineseAcademy of Sciences, Shanghai 200031, China |
| 推荐引用方式 GB/T 7714 | Zhang AM,Bi R,Yao YG[*],et al. The OPA1 GeneMutations Are Frequent in Han Chinese Patients with Suspected Optic Neuropathy[J]. Mol Neurobiol,2016,**(**):Online. |
| APA | Zhang AM,Bi R,Yao YG[*],Hu QX,Fan Y,&Zhang QJ.(2016).The OPA1 GeneMutations Are Frequent in Han Chinese Patients with Suspected Optic Neuropathy.Mol Neurobiol,**(**),Online. |
| MLA | Zhang AM,et al."The OPA1 GeneMutations Are Frequent in Han Chinese Patients with Suspected Optic Neuropathy".Mol Neurobiol **.**(2016):Online. |
入库方式： OAI收割
来源：昆明动物研究所
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