{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:57:20Z","timestamp":1787068640484,"version":"build-2736575974"},"reference-count":47,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"8","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Trans. Vis. Sci. Tech."],"published-print":{"date-parts":[[2020,7,8]]},"DOI":"10.1167\/tvst.9.8.11","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T14:31:45Z","timestamp":1594218705000},"page":"11","source":"Crossref","is-referenced-by-count":17,"title":["Mutation Screening of mtDNA Combined Targeted Exon Sequencing in a Cohort With Suspected Hereditary Optic Neuropathy"],"prefix":"10.1167","volume":"9","author":[{"given":"Jian-Kang","family":"Li","sequence":"first","affiliation":[{"name":"BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China"},{"name":"Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong"},{"name":"BGI-Shenzhen, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China"},{"name":"BGI-Shenzhen, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Juan","family":"Gao","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye, Ear, Nose and Throat Hospital, College of Medicine, Fudan University, Shanghai, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Fang","family":"Qu","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Tiantan Xili Dongcheng District, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Yuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye, Ear, Nose and Throat Hospital, College of Medicine, Fudan University, Shanghai, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Hai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye, Ear, Nose and Throat Hospital, College of Medicine, Fudan University, Shanghai, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Li","family":"Li","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Tiantan Xili Dongcheng District, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China"},{"name":"BGI-Shenzhen, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Qiu","sequence":"additional","affiliation":[{"name":"BGI-Shenzhen, Shenzhen, China"},{"name":"MGI, BGI-Shenzhen, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu-Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Computer Science, City University of Hong Kong, Kowloon, Hong Kong"},{"name":"BGI-Shenzhen, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"National Institutes for Food and Drug Control, Tiantan Xili Dongcheng District, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hong","family":"Wu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye, Ear, Nose and Throat Hospital, College of Medicine, Fudan University, Shanghai, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"BGI-Shenzhen, Shenzhen, China"},{"name":"MGI, BGI-Shenzhen, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1586\/ern.13.19","article-title":"Genetic and phenotypic variability of optic neuropathies","volume":"13","author":"Neuhann","year":"2013","journal-title":"Expert Rev Neurother"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/79936","article-title":"Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy","volume":"26","author":"Delettre","year":"2000","journal-title":"Nat Genet"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"e110","DOI":"10.1136\/jmg.2003.016576","article-title":"OPA3 gene mutations responsible for autosomal dominant optic atrophy and cataract","volume":"41","author":"Reynier","year":"2004","journal-title":"J Med Genet"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.preteyeres.2003.10.003","article-title":"Mitochondrial dysfunction as a cause of optic neuropathies","volume":"23","author":"Carelli","year":"2004","journal-title":"Prog Retin Eye Res"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.ajhg.2009.03.003","article-title":"TMEM126A, encoding a mitochondrial protein, is mutated in autosomal-recessive nonsyndromic optic atrophy","volume":"84","author":"Hanein","year":"2009","journal-title":"Am J Human Genet"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1136\/jmedgenet-2014-102532","article-title":"Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy","volume":"51","author":"Metodiev","year":"2014","journal-title":"J Med Genet"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1007\/s12031-019-01319-7","article-title":"Whole exon sequencing identifies two novel mutations in the reticulon 4\u2013interacting protein 1 gene in a Chinese family with autosomal recessive optic neuropathies","volume":"68","author":"Zou","year":"2019","journal-title":"J Mol Neurosci"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.preteyeres.2006.05.002","article-title":"Leber's hereditary optic neuropathy: a multifactorial disease","volume":"25","author":"Yen","year":"2006","journal-title":"Prog Retin Eye Res"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.mcn.2012.08.004","article-title":"The optic nerve: a \u201cmito-window\u201d on mitochondrial neurodegeneration","volume":"55","author":"Maresca","year":"2013","journal-title":"Mol Cell Neurosci"},{"key":"bib10","first-page":"77","article-title":"Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation.","volume":"57","author":"Harding","year":"1995","journal-title":"Am J Human Genet"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1126\/science.3201231","article-title":"Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy","volume":"242","author":"Wallace","year":"1988","journal-title":"Science"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"D823","DOI":"10.1093\/nar\/gkl927","article-title":"An enhanced MITOMAP with a global mtDNA mutational phylogeny","volume":"35","author":"Ruiz-Pesini","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.ymgme.2010.07.014","article-title":"Mitochondrial haplogroup M9a specific variant ND1 T3394C may have a modifying role in the phenotypic expression of the LHON-associated ND4 G11778A mutation","volume":"101","author":"Zhang","year":"2010","journal-title":"Mol Genet Metab"},{"key":"bib14","first-page":"434","article-title":"Mitochondrial haplogroup D4j specific variant m.11696G?>?a(MT-ND4) may increase the penetrance and expressivity of the LHON-associated m.11778G?>?a mutation in Chinese pedigrees","volume":"28","author":"Xie","year":"2017","journal-title":"DNA Seq"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1016\/j.ophtha.2009.12.038","article-title":"The prevalence and natural history of dominant optic atrophy due to OPA1 mutations","volume":"117","author":"Yu-Wai-Man","year":"2010","journal-title":"Ophthalmology"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1750-1172-7-46","article-title":"Dominant optic atrophy","volume":"7","author":"Lenaers","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1016\/S0006-291X(02)02874-7","article-title":"Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria","volume":"300","author":"Satoh","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.ymgme.2010.03.005","article-title":"OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria","volume":"100","author":"Huizing","year":"2010","journal-title":"Mol Genet Metab"},{"key":"bib19","first-page":"1715","article-title":"A comprehensive survey of mutations in the opa1 gene in patients with autosomal dominant optic atrophy","volume":"43","author":"Thiselton","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"E692","DOI":"10.1002\/humu.v30:7","article-title":"Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations","volume":"30","author":"Ferre","year":"2009","journal-title":"Hum Mutat"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/humu.2015.36.issue-1","article-title":"Improved locus-specific database for OPA1 mutations allows inclusion of advanced clinical data","volume":"36","author":"Ferr\u00e9","year":"2015","journal-title":"Human Mutat"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"e16078","DOI":"10.7554\/eLife.16078","article-title":"Homozygous YME1L1mutation causes mitochondriopathy with optic atrophy and mitochondrial network fragmentation","volume":"5","author":"Hartmann","year":"2016","journal-title":"Elife"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1001\/jamaneurol.2017.2065","article-title":"Neurologic phenotypes associated with mutations in RTN4IP1 (OPA10) in children and young adults","volume":"75","author":"Charif","year":"2018","journal-title":"JAMA Neurol"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1016\/j.ajhg.2015.09.012","article-title":"Recessive mutations in RTN4IP1 cause isolated and syndromic optic neuropathies","volume":"97","author":"Claire","year":"2015","journal-title":"Am J Human Genet"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1007\/s00401-016-1625-2","article-title":"A neurodegenerative perspective on mitochondrial optic neuropathies","volume":"132","author":"Yu-Wai-Man","year":"2016","journal-title":"Acta Neuropathol"},{"key":"bib26","first-page":"650","article-title":"Nonsense mutation in TMEM126A causing autosomal recessive optic atrophy and auditory neuropathy","volume":"16","author":"Meyer","year":"2010","journal-title":"Mol Vis"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/j.ophtha.2019.04.038","article-title":"Genetic and clinical findings in a large cohort of Chinese patients with suspected retinitis pigmentosa","volume":"126","author":"Gao","year":"2019","journal-title":"Ophthalmology"},{"key":"bib28","doi-asserted-by":"crossref","first-page":"e00948","DOI":"10.1002\/mgg3.948","article-title":"A start codon mutation of the TSPAN12 gene in Chinese families causes clinical heterogeneous familial exudative vitreoretinopathy","volume":"7","author":"Li","year":"2019","journal-title":"Mol Genet Genomic Med"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"R27","DOI":"10.1093\/hmg\/ddt384","article-title":"Databases of genomic variation and phenotypes: existing resources and future needs","volume":"22","author":"Johnston","year":"2013","journal-title":"Human Mol Genet"},{"key":"bib30","first-page":"Unit1.13","article-title":"The Human Gene Mutation Database (HGMD) and its exploitation in the fields of personalized genomics and molecular evolution","volume":"Chapter 1","author":"Stenson","year":"2012","journal-title":"Curr Protoc Bioinformatics"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1086\/519394","article-title":"Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA\u2013haplogroup background","volume":"81","author":"Hudson","year":"2007","journal-title":"Am J Human Genet"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.ajhg.2008.11.002","article-title":"Mitochondrial DNA haplogroups M7b1'2 and M8a affect clinical expression of Leber hereditary optic neuropathy in Chinese families with the m.11778G?A mutation","volume":"83","author":"Ji Y, Zhang AM, Jia Xi","year":"2008","journal-title":"Am J Human Genet"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"6987","DOI":"10.1167\/iovs.14-14953","article-title":"Mutation screening of mitochondrial DNA as well as OPA1 and OPA3 in a Chinese cohort with suspected hereditary optic atrophy","volume":"55","author":"Chen","year":"2014","journal-title":"Invest Ophthal Vis Sci"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12881-019-0795-x","article-title":"Novel likely pathogenic variants in TMEM126A identified in non-syndromic autosomal recessive optic atrophy: two case reports","volume":"20","author":"Kloth","year":"2019","journal-title":"BMC Med Genet"},{"key":"bib35","first-page":"1107","article-title":"Haplotype and phylogenetic analyses suggest that one European-specific mtDNA background plays a role in the expression of Leber hereditary optic neuropathy by increasing the penetrance of the primary mutations 11778 and 14484","volume":"60","author":"Torroni","year":"1997","journal-title":"Am J Human Genet"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.ophtha.2010.07.029","article-title":"Genetic screening for OPA1 and OPA3 mutations in patients with suspected inherited optic neuropathies","volume":"118","author":"Yu-Wai-Man","year":"2011","journal-title":"Ophthalmology"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1007\/s10038-006-0032-2","article-title":"Molecular epidemiology of mtDNA mutations in 903 Chinese families suspected with Leber hereditary optic neuropathy","volume":"51","author":"Jia","year":"2006","journal-title":"J Human Genet"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1167\/iovs.13-13011","article-title":"Frequency and spectrum of mitochondrial ND6 mutations in 1218 Han Chinese subjects with Leber's hereditary optic neuropathy","volume":"55","author":"Liang","year":"2014","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/1471-2350-13-65","article-title":"Dominant optic atrophy in Denmark\u2013report of 15 novel mutations in OPA1, using a strategy with a detection rate of 90%","volume":"13","author":"Almind","year":"2012","journal-title":"BMC Med Genet"},{"key":"bib40","first-page":"912","article-title":"Targeted next-generation sequencing extends the mutational spectrums for OPA1 mutations in Chinese families with optic atrophy","volume":"25","author":"Wang Y, Xu M, Liu X","year":"2019","journal-title":"Mol Vis"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"S30","DOI":"10.1016\/j.mito.2015.07.086","article-title":"Modeling autosomal dominant optic atrophy using induced pluripotent stem cells and identifying potential therapeutic targets","volume":"24","author":"Chen","year":"2015","journal-title":"Mitochondrion"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.ajo.2006.12.038","article-title":"Autosomal dominant optic atrophy: penetrance and expressivity in patients with OPA1 mutations","volume":"143","author":"Cohn","year":"2007","journal-title":"Am J Ophthalmol"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.ophtha.2005.10.054","article-title":"Novel mutations in the OPA1 gene and associated clinical features in Japanese patients with optic atrophy","volume":"113","author":"Nakamura","year":"2006","journal-title":"Ophthalmology"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/79944","article-title":"OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28","volume":"26","author":"Alexander","year":"2000","journal-title":"Nat Genet"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1080\/13816810.2018.1466337","article-title":"Clinical and genetic features of eight Chinese autosomal-dominant optic atrophy pedigrees with six novel OPA1 pathogenic variants","volume":"39","author":"Li","year":"2018","journal-title":"Ophthalmic Genet"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1111\/aos.2017.95.issue-4","article-title":"OPA1 analysis in an international series of probands with bilateral optic atrophy","volume":"95","author":"Liskova","year":"2017","journal-title":"Acta Ophthalmol"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1212\/01.wnl.0000335931.54095.0a","article-title":"OPA1 in multiple mitochondrial DNA deletion disorders","volume":"71","author":"Stewart","year":"2008","journal-title":"Neurology"}],"container-title":["Translational Vision Science & Technology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/tvst.arvojournals.org\/article.aspx?articleid=2770264","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T14:31:49Z","timestamp":1594218709000},"score":1,"resource":{"primary":{"URL":"https:\/\/tvst.arvojournals.org\/article.aspx?articleid=2770264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,8]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,7,1]]}},"URL":"https:\/\/doi.org\/10.1167\/tvst.9.8.11","relation":{},"ISSN":["2164-2591"],"issn-type":[{"value":"2164-2591","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7,8]]}}}