{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:35:26Z","timestamp":1793316926695,"version":"4.5.0"},"reference-count":50,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001108","name":"Ophthalmic Research Institute of Australia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1023911"],"award-info":[{"award-number":["1023911"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1116360"],"award-info":[{"award-number":["1116360"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The American Journal of Human Genetics"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1016\/j.ajhg.2021.09.015","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T10:57:23Z","timestamp":1634813843000},"page":"2159-2170","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":67,"title":["Establishing risk of vision loss in Leber hereditary optic neuropathy"],"prefix":"10.1016","volume":"108","author":[{"given":"M. Isabel G.","family":"Lopez Sanchez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa S.","family":"Kearns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra E.","family":"Staffieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Clarke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myra B.","family":"McGuinness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wafaa","family":"Meteoukki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan B.","family":"Ruddle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare L.","family":"Fraser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex W.","family":"Hewitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Howell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7914-4709","authenticated-orcid":false,"given":"David A.","family":"Mackey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ajhg.2021.09.015_bib1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pharmthera.2016.06.004","article-title":"Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies","volume":"165","author":"Lopez Sanchez","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.ajhg.2021.09.015_bib2","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1126\/science.3201231","article-title":"Mitochondrial DNA mutation associated with Leber\u2019s hereditary optic neuropathy","volume":"242","author":"Wallace","year":"1988","journal-title":"Science"},{"key":"10.1016\/j.ajhg.2021.09.015_bib3","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1016\/0006-291X(92)90479-5","article-title":"An ND-6 mitochondrial DNA mutation associated with Leber hereditary optic neuropathy","volume":"187","author":"Johns","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ajhg.2021.09.015_bib4","first-page":"1218","article-title":"A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology","volume":"51","author":"Mackey","year":"1992","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib5","first-page":"939","article-title":"Leber hereditary optic neuropathy: identification of the same mitochondrial ND1 mutation in six pedigrees","volume":"49","author":"Howell","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib6","first-page":"1147","article-title":"A new mtDNA mutation associated with Leber hereditary optic neuroretinopathy","volume":"48","author":"Huoponen","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib7","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/ajmg.a.20135","article-title":"Low penetrance of the 14484 LHON mutation when it arises in a non-haplogroup J mtDNA background","volume":"119A","author":"Howell","year":"2003","journal-title":"Am. J. Med. Genet. A."},{"key":"10.1016\/j.ajhg.2021.09.015_bib8","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1086\/519394","article-title":"Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background","volume":"81","author":"Hudson","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib9","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. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib10","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1093\/brain\/awp158","article-title":"Gene-environment interactions in Leber hereditary optic neuropathy","volume":"132","author":"Kirkman","year":"2009","journal-title":"Brain"},{"key":"10.1016\/j.ajhg.2021.09.015_bib11","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/sj.eye.6700362","article-title":"Leber\u2019s hereditary optic neuropathy triggered by antiretroviral therapy for human immunodeficiency virus","volume":"17","author":"Mackey","year":"2003","journal-title":"Eye (Lond.)"},{"key":"10.1016\/j.ajhg.2021.09.015_bib12","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/j.1442-9071.2010.02240.x","article-title":"Antituberculosis medication as a possible epigenetic factor of Leber\u2019s hereditary optic neuropathy","volume":"38","author":"Seo","year":"2010","journal-title":"Clin. Exp. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib13","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.mito.2020.07.003","article-title":"OXPHOS bioenergetic compensation does not explain disease penetrance in Leber hereditary optic neuropathy","volume":"54","author":"Lopez Sanchez","year":"2020","journal-title":"Mitochondrion"},{"key":"10.1016\/j.ajhg.2021.09.015_bib14","first-page":"486","article-title":"Optic atrophy in Leber hereditary optic neuroretinopathy is probably determined by an X-chromosomal gene closely linked to DXS7","volume":"48","author":"Vilkki","year":"1991","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib15","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1442-9071.1992.tb00937.x","article-title":"Leber hereditary optic neuropathy in Australia","volume":"20","author":"Mackey","year":"1992","journal-title":"Aust. N. Z. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib16","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/sj.ejhg.5201828","article-title":"Epidemiology and penetrance of Leber hereditary optic neuropathy in Finland","volume":"15","author":"Puomila","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib17","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ophtha.2008.10.022","article-title":"Extremely low penetrance of Leber\u2019s hereditary optic neuropathy in 8 Han Chinese families carrying the ND4 G11778A mutation","volume":"116","author":"Qu","year":"2009","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ajhg.2021.09.015_bib18","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.ophtha.2019.11.014","article-title":"Demographics of a Large International Population of Patients Affected by Leber\u2019s Hereditary Optic Neuropathy","volume":"127","author":"Poincenot","year":"2020","journal-title":"Ophthalmology"},{"key":"10.1016\/j.ajhg.2021.09.015_bib19","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/S0002-9394(14)70337-X","article-title":"Tobacco amblyopia","volume":"117","author":"Mackey","year":"1994","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib20","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0002-9394(03)00099-0","article-title":"Extensive investigation of a large Brazilian pedigree of 11778\/haplogroup J Leber hereditary optic neuropathy","volume":"136","author":"Sadun","year":"2003","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib21","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s10897-005-9014-3","article-title":"A new definition of Genetic Counseling: National Society of Genetic Counselors\u2019 Task Force report","volume":"15","author":"Resta","year":"2006","journal-title":"J.\u00a0Genet. Couns."},{"key":"10.1016\/j.ajhg.2021.09.015_bib22","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1442-9071.1996.tb01545.x","article-title":"Sporadic Leber hereditary optic neuropathy in Australia and New Zealand","volume":"24","author":"Chan","year":"1996","journal-title":"Aust. N. Z. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib23","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1001\/archopht.1983.01040020061011","article-title":"Ophthalmoscopic findings in Leber\u2019s hereditary optic neuropathy. II. The fundus findings in the affected family members","volume":"101","author":"Nikoskelainen","year":"1983","journal-title":"Arch. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib24","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/S0002-9394(14)76784-4","article-title":"The clinical characteristics of pedigrees of Leber\u2019s hereditary optic neuropathy with the 11778 mutation","volume":"111","author":"Newman","year":"1991","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib25","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1086\/346066","article-title":"The epidemiology of Leber hereditary optic neuropathy in the North East of England","volume":"72","author":"Yu-Wai-Man","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib26","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1086\/375537","article-title":"Sequence analysis of the mitochondrial genomes from Dutch pedigrees with Leber hereditary optic neuropathy","volume":"72","author":"Howell","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib27","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1101\/gr.2228504","article-title":"The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection","volume":"14","author":"Maitra","year":"2004","journal-title":"Genome Res."},{"key":"10.1016\/j.ajhg.2021.09.015_bib28","doi-asserted-by":"crossref","first-page":"1.23.21","DOI":"10.1002\/0471250953.bi0123s44","article-title":"mtDNA Variation and Analysis Using Mitomap and Mitomaster","volume":"44","author":"Lott","year":"2013","journal-title":"Curr. Protoc. Bioinformatics"},{"key":"10.1016\/j.ajhg.2021.09.015_bib29","doi-asserted-by":"crossref","first-page":"E386","DOI":"10.1002\/humu.20921","article-title":"Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation","volume":"30","author":"van Oven","year":"2009","journal-title":"Hum. Mutat."},{"key":"10.1016\/j.ajhg.2021.09.015_bib30","first-page":"53","article-title":"Leber Hereditary Optic Neuropathy and Longitudinally Extensive Transverse Myelitis","volume":"42","author":"Bursle","year":"2018","journal-title":"JIMD Rep."},{"key":"10.1016\/j.ajhg.2021.09.015_bib31","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1136\/bjo.2006.099333","article-title":"The role of the Met98Lys optineurin variant in inherited optic nerve diseases","volume":"90","author":"Craig","year":"2006","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib32","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1086\/301675","article-title":"mtDNA mutations that cause optic neuropathy: how do we know?","volume":"62","author":"Howell","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib33","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/00041327-200212000-00002","article-title":"Lightning strikes twice: Leber hereditary optic neuropathy families with two pathogenic mtDNA mutations","volume":"22","author":"Howell","year":"2002","journal-title":"J.\u00a0Neuroophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib34","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/eye.1994.102","article-title":"Three subgroups of patients from the United Kingdom with Leber hereditary optic neuropathy","volume":"8","author":"Mackey","year":"1994","journal-title":"Eye (Lond.)"},{"key":"10.1016\/j.ajhg.2021.09.015_bib35","first-page":"481","article-title":"Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy","volume":"59","author":"Mackey","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib36","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1167\/iovs.06-1470","article-title":"Heritable features of the optic disc: a novel twin method for determining genetic significance","volume":"48","author":"Hewitt","year":"2007","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ajhg.2021.09.015_bib37","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/0140-6736(93)91105-U","article-title":"Blindness in offspring of women blinded by Leber\u2019s hereditary optic neuropathy","volume":"341","author":"Mackey","year":"1993","journal-title":"Lancet"},{"key":"10.1016\/j.ajhg.2021.09.015_bib38","doi-asserted-by":"crossref","first-page":"253","DOI":"10.5694\/j.1326-5377.1915.tb22568.x","article-title":"Leber\u2019s disease","volume":"1","author":"Hogg","year":"1915","journal-title":"Medical Journal of Australia"},{"key":"10.1016\/j.ajhg.2021.09.015_bib39","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1136\/bjo.22.3.129","article-title":"The significance of heredity in ophthalmology. Preliminary survey of hereditary eye diseases in tasmania","volume":"22","author":"Hamilton","year":"1938","journal-title":"Br. J. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib40","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1167\/iovs.15-18306","article-title":"Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population","volume":"57","author":"Rosenberg","year":"2016","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.ajhg.2021.09.015_bib41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF00573524","article-title":"Leber\u2019s disease in the netherlands","volume":"17","author":"Vansenus","year":"1963","journal-title":"Doc. Ophthalmol."},{"key":"10.1016\/j.ajhg.2021.09.015_bib42","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/BF02267075","article-title":"No evidence for \u2018skewed\u2019 inactivation of the X-chromosome as cause of Leber\u2019s hereditary optic neuropathy in female carriers","volume":"97","author":"Oostra","year":"1996","journal-title":"Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib43","first-page":"135","article-title":"Hereditary infantile optic atrophy with dominant transmission; preliminary report","volume":"3","author":"Kjer","year":"1956","journal-title":"Dan. Med. Bull."},{"key":"10.1016\/j.ajhg.2021.09.015_bib44","series-title":"Hereditary Optic Atrophy Leber\u2019s Disease: By Julia Bell. With Frontispiece Portrait of Leber and Pedigree Plates 48-63, Figs","first-page":"704","author":"Bell","year":"1931"},{"key":"10.1016\/j.ajhg.2021.09.015_bib45","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1086\/302049","article-title":"Low-penetrance branches in matrilineal pedigrees with Leber hereditary optic neuropathy","volume":"63","author":"Howell","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.ajhg.2021.09.015_bib46","first-page":"169","article-title":"A very large Brazilian pedigree with 11778 Leber\u2019s hereditary optic neuropathy","volume":"100","author":"Sadun","year":"2002","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"10.1016\/j.ajhg.2021.09.015_bib47","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/s41467-020-20851-4","article-title":"Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries","volume":"12","author":"Gharahkhani","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ajhg.2021.09.015_bib48","doi-asserted-by":"crossref","first-page":"e138267","DOI":"10.1172\/JCI138267","article-title":"Impaired complex I repair causes recessive Leber\u2019s hereditary optic neuropathy","volume":"131","author":"Stenton","year":"2021","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ajhg.2021.09.015_bib49","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1172\/JCI134965","article-title":"PRICKLE3 linked to ATPase biogenesis manifested Leber\u2019s hereditary optic neuropathy","volume":"130","author":"Yu","year":"2020","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.ajhg.2021.09.015_bib50","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/ejhg.2017.139","article-title":"22 Years of predictive testing for Huntington\u2019s disease: the experience of the UK Huntington\u2019s Prediction Consortium","volume":"25","author":"Baig","year":"2017","journal-title":"Eur. J. Hum. Genet."}],"container-title":["The American Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929721003517?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0002929721003517?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:20:53Z","timestamp":1762078853000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0002929721003517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["S0002929721003517"],"URL":"https:\/\/doi.org\/10.1016\/j.ajhg.2021.09.015","relation":{},"ISSN":["0002-9297"],"issn-type":[{"value":"0002-9297","type":"print"}],"subject":[],"published":{"date-parts":[[2021,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Establishing risk of vision loss in Leber hereditary optic neuropathy","name":"articletitle","label":"Article Title"},{"value":"The American Journal of Human Genetics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ajhg.2021.09.015","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s).","name":"copyright","label":"Copyright"}]}}