title: The OPA1 Gene Mutations Are Frequent in Han Chinese Patients with Suspected Optic Neuropathy.
abstract: While many patients with hereditary optic neuropathies are caused by mitochondrial DNA (mtDNA) mutations of Leber's hereditary optic neuropathy (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 screening OPA1 mutation is needed for clinical diagnosis of patients with suspected optic neuropathy.
authors: 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.|Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China.
authors: A-Mei
authors: AM
authors: Zhang
authors: 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.
authors: Rui
authors: R
authors: Bi
authors: 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.
authors: Qiu-Xiang
authors: QX
authors: Hu
authors: 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.
authors: Yu
authors: Y
authors: Fan
authors: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors: Qingjiong
authors: Q
authors: Zhang
authors: 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. yaoyg@mail.kiz.ac.cn.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. yaoyg@mail.kiz.ac.cn.
authors: Yong-Gang
authors: YG
authors: Yao
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009901:Optic Nerve Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human
keywords: Han Chinese; Mitochondrial dysfunction; OPA1; Pathogenicity; Suspected optic neuropathy