{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:00:25Z","timestamp":1793714425091,"version":"4.6.1"},"reference-count":133,"publisher":"BMJ","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2002,3]]},"abstract":"<jats:p>Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that preferentially causes blindness in young adult males, affecting about 1 in 25 000 of the British population. It is characterised by bilateral subacute loss of central vision owing to focal degeneration of the retinal ganglion cell layer and optic nerve. Over 95% of LHON cases are primarily the result of one of three mitochondrial DNA (mtDNA) point mutations, G3460A, G11778A, and T14484C, which all involve genes encoding complex I subunits of the respiratory chain. An intriguing feature of LHON is that only \u223c50% of males and \u223c10% of females who harbour a pathogenic mtDNA mutation actually develop the optic neuropathy. This marked incomplete penetrance and gender bias imply that additional mitochondrial and\/or nuclear genetic factors must be modulating the phenotypic expression of LHON. It is also likely that environmental factors contribute to the onset of visual failure. However, these secondary precipitating factors remain poorly defined at present. In this review, we describe the natural history of this optic nerve disorder and highlight issues relating to clinical diagnosis, management, and genetic counselling. We also discuss the findings of recently published studies and the light they shed on the complex aetiology and pathophysiology of LHON.<\/jats:p>","DOI":"10.1136\/jmg.39.3.162","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T06:30:44Z","timestamp":1027751444000},"page":"162-169","source":"Crossref","is-referenced-by-count":398,"title":["Leber hereditary optic neuropathy"],"prefix":"10.1136","volume":"39","author":[{"given":"P Y W","family":"Man","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D M","family":"Turnbull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P F","family":"Chinnery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2002,3,1]]},"reference":[{"key":"2025101801062489000_39.3.162.1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01694557"},{"key":"2025101801062489000_39.3.162.2","unstructured":"Bell J. Hereditary optic atrophy (Leber's disease). In: Pearson K, ed. The treasury of human inheritance. Cambridge: Cambridge University Press, 1931:345-423."},{"key":"2025101801062489000_39.3.162.3","doi-asserted-by":"publisher","DOI":"10.1007\/BF02982530"},{"key":"2025101801062489000_39.3.162.4","first-page":"1","volume":"21","year":"1944","journal-title":"Acta Ophthalmol"},{"key":"2025101801062489000_39.3.162.5","doi-asserted-by":"publisher","DOI":"10.1007\/BF00573524"},{"key":"2025101801062489000_39.3.162.6","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1111\/j.1755-3768.1968.tb02490.x","volume":"46","year":"1968","journal-title":"Acta Ophthalmol"},{"key":"2025101801062489000_39.3.162.7","first-page":"481","volume":"59","year":"1996","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.8","doi-asserted-by":"publisher","DOI":"10.1080\/02713689808951221"},{"key":"2025101801062489000_39.3.162.9","first-page":"77","volume":"57","year":"1995","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.10","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1212\/WNL.50.2.417","volume":"50","year":"1998","journal-title":"Neurology"},{"key":"2025101801062489000_39.3.162.11","doi-asserted-by":"publisher","DOI":"10.1086\/302716"},{"key":"2025101801062489000_39.3.162.12","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/124.1.209"},{"key":"2025101801062489000_39.3.162.13","doi-asserted-by":"publisher","DOI":"10.1126\/science.3201231"},{"key":"2025101801062489000_39.3.162.14","first-page":"1147","volume":"48","year":"1991","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.15","first-page":"939","volume":"49","year":"1991","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.16","first-page":"1218","volume":"51","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.17","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(92)90479-5"},{"key":"2025101801062489000_39.3.162.18","first-page":"959","volume":"53","year":"1993","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.13.6206"},{"key":"2025101801062489000_39.3.162.20","doi-asserted-by":"publisher","DOI":"10.1086\/301675"},{"key":"2025101801062489000_39.3.162.21","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.6660"},{"key":"2025101801062489000_39.3.162.22","first-page":"703","volume":"58","year":"1996","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.23","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200008)48:2<188::AID-ANA8>3.0.CO;2-P"},{"key":"2025101801062489000_39.3.162.24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1442-9071.1992.tb00937.x","volume":"20","year":"1992","journal-title":"Aust NZ J Ophthalmol"},{"key":"2025101801062489000_39.3.162.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(14)76784-4"},{"key":"2025101801062489000_39.3.162.26","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1992.01080230077025"},{"key":"2025101801062489000_39.3.162.27","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1993.01090040087038"},{"key":"2025101801062489000_39.3.162.28","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1212\/WNL.49.4.1136","volume":"49","year":"1997","journal-title":"Neurology"},{"key":"2025101801062489000_39.3.162.29","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.32.2.81"},{"key":"2025101801062489000_39.3.162.30","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/S0161-6420(96)30665-9","volume":"103","year":"1996","journal-title":"Ophthalmology"},{"key":"2025101801062489000_39.3.162.31","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/118.2.319"},{"key":"2025101801062489000_39.3.162.32","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/115.4.979"},{"key":"2025101801062489000_39.3.162.33","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(95)00287-C"},{"key":"2025101801062489000_39.3.162.34","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410360121"},{"key":"2025101801062489000_39.3.162.35","doi-asserted-by":"publisher","DOI":"10.1007\/s004170050243"},{"key":"2025101801062489000_39.3.162.36","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/j.1600-0404.1995.tb07016.x","volume":"91","year":"1995","journal-title":"Acta Neurol Scand"},{"key":"2025101801062489000_39.3.162.37","doi-asserted-by":"publisher","DOI":"10.1007\/s004150070153"},{"key":"2025101801062489000_39.3.162.38","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(95)00021-S"},{"key":"2025101801062489000_39.3.162.39","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(95)00286-B"},{"key":"2025101801062489000_39.3.162.40","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90272-0"},{"key":"2025101801062489000_39.3.162.41","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.5.1481"},{"key":"2025101801062489000_39.3.162.42","doi-asserted-by":"publisher","DOI":"10.3109\/13816819509059971"},{"key":"2025101801062489000_39.3.162.43","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.59.2.160"},{"key":"2025101801062489000_39.3.162.44","first-page":"1427","volume":"339","year":"1992","journal-title":"Lancet"},{"key":"2025101801062489000_39.3.162.45","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1399-0004.1996.tb02732.x","volume":"50","year":"1996","journal-title":"Clin Genet"},{"key":"2025101801062489000_39.3.162.46","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)92830-4"},{"key":"2025101801062489000_39.3.162.47","first-page":"935","volume":"48","year":"1991","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.48","first-page":"121","volume":"2","year":"1994","journal-title":"Clin Neurosci"},{"key":"2025101801062489000_39.3.162.49","first-page":"231","volume":"10","year":"1990","journal-title":"J Clin Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.50","first-page":"89","volume":"12","year":"1992","journal-title":"J Clin Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.51","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1159\/000116781","volume":"32","year":"1992","journal-title":"Eur Neurol"},{"key":"2025101801062489000_39.3.162.52","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1136\/jnnp.64.1.124","volume":"64","year":"1998","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2025101801062489000_39.3.162.53","first-page":"238","volume":"19","year":"1999","journal-title":"J Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.54","first-page":"A320","volume":"54","year":"2000","journal-title":"Neurology"},{"key":"2025101801062489000_39.3.162.55","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1001\/archopht.116.7.911","volume":"116","year":"1998","journal-title":"Arch Ophthalmol"},{"key":"2025101801062489000_39.3.162.56","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3109\/01658109409024039","volume":"14","year":"1994","journal-title":"J Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.57","first-page":"185","volume":"34","year":"1958","journal-title":"Am J Ophthalmol"},{"key":"2025101801062489000_39.3.162.58","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/89.1.15"},{"key":"2025101801062489000_39.3.162.59","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6989(96)00167-8"},{"key":"2025101801062489000_39.3.162.60","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1056\/NEJM198905183202007","volume":"320","year":"1989","journal-title":"N Engl J Med"},{"key":"2025101801062489000_39.3.162.61","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(91)80886-8"},{"key":"2025101801062489000_39.3.162.62","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300511"},{"key":"2025101801062489000_39.3.162.63","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(94)90055-8"},{"key":"2025101801062489000_39.3.162.64","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00971-6"},{"key":"2025101801062489000_39.3.162.65","first-page":"1501","volume":"57","year":"1995","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.66","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2563"},{"key":"2025101801062489000_39.3.162.67","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1740"},{"key":"2025101801062489000_39.3.162.68","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.58.5.640"},{"key":"2025101801062489000_39.3.162.69","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/j.1432-1033.1996.0201u.x","volume":"239","year":"1996","journal-title":"Eur J Biochem"},{"key":"2025101801062489000_39.3.162.70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.22.13155"},{"key":"2025101801062489000_39.3.162.71","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.6.1623"},{"key":"2025101801062489000_39.3.162.72","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440208"},{"key":"2025101801062489000_39.3.162.73","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(99)00088-X"},{"key":"2025101801062489000_39.3.162.74","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006476200"},{"key":"2025101801062489000_39.3.162.75","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1212\/WNL.41.8.1211","volume":"41","year":"1991","journal-title":"Neurology"},{"key":"2025101801062489000_39.3.162.76","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1212\/WNL.45.7.1364","volume":"45","year":"1995","journal-title":"Neurology"},{"key":"2025101801062489000_39.3.162.77","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420407"},{"key":"2025101801062489000_39.3.162.78","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.83.2.231"},{"key":"2025101801062489000_39.3.162.79","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S0021-9258(18)65313-X","volume":"220","year":"1956","journal-title":"J Biol Chem"},{"key":"2025101801062489000_39.3.162.80","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1523\/JNEUROSCI.04-10-02445.1984","volume":"4","year":"1984","journal-title":"J Neurosci"},{"key":"2025101801062489000_39.3.162.81","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.70.3.359"},{"key":"2025101801062489000_39.3.162.82","first-page":"3","volume":"74","year":"1996","journal-title":"Acta Orthop Scand"},{"key":"2025101801062489000_39.3.162.83","doi-asserted-by":"publisher","DOI":"10.1038\/79936"},{"key":"2025101801062489000_39.3.162.84","doi-asserted-by":"publisher","DOI":"10.1038\/79944"},{"key":"2025101801062489000_39.3.162.85","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9539"},{"key":"2025101801062489000_39.3.162.86","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(98)01490-1"},{"key":"2025101801062489000_39.3.162.87","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80391-3"},{"key":"2025101801062489000_39.3.162.88","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1755-3768.1985.tb01526.x","volume":"63","year":"1985","journal-title":"Acta Ophtalmol"},{"key":"2025101801062489000_39.3.162.89","first-page":"115","volume":"2","year":"1994","journal-title":"Clin Neurosci"},{"key":"2025101801062489000_39.3.162.90","first-page":"138","volume":"2","year":"1994","journal-title":"Clin Neurosci"},{"key":"2025101801062489000_39.3.162.91","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1159\/000267739","volume":"27","year":"1995","journal-title":"Ophthal Res"},{"key":"2025101801062489000_39.3.162.92","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1993.01090110052022"},{"key":"2025101801062489000_39.3.162.93","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320420208"},{"key":"2025101801062489000_39.3.162.94","first-page":"2561","volume":"33","year":"1992","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"2025101801062489000_39.3.162.95","first-page":"219","volume":"13","year":"1992","journal-title":"Ophthal Pediatr Genet"},{"key":"2025101801062489000_39.3.162.96","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.80.10.915"},{"key":"2025101801062489000_39.3.162.97","first-page":"81","volume":"18","year":"1998","journal-title":"J Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.98","unstructured":"Chinnery PF, Andrews RM, Turnbull DM, Howell N. Leber hereditary optic neuropathy: does heteroplasmy influence the inheritance and expression of the G11778A mitochondrial DNA mutation? Am J Med Genet (in press)."},{"key":"2025101801062489000_39.3.162.99","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91567-V"},{"key":"2025101801062489000_39.3.162.100","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)92088-2"},{"key":"2025101801062489000_39.3.162.101","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.2321"},{"key":"2025101801062489000_39.3.162.102","doi-asserted-by":"publisher","DOI":"10.1007\/BF00763098"},{"key":"2025101801062489000_39.3.162.103","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380060405"},{"key":"2025101801062489000_39.3.162.104","first-page":"1107","volume":"60","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.105","first-page":"381","volume":"60","year":"1997","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.106","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/genetics\/140.1.285","volume":"140","year":"1995","journal-title":"Genetics"},{"key":"2025101801062489000_39.3.162.107","doi-asserted-by":"publisher","DOI":"10.1007\/s100380170110"},{"key":"2025101801062489000_39.3.162.108","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/123.9.1896"},{"key":"2025101801062489000_39.3.162.109","doi-asserted-by":"publisher","DOI":"10.1007\/BF00212020"},{"key":"2025101801062489000_39.3.162.110","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.18.8198"},{"key":"2025101801062489000_39.3.162.111","doi-asserted-by":"publisher","DOI":"10.1007\/BF01247331"},{"key":"2025101801062489000_39.3.162.112","doi-asserted-by":"publisher","DOI":"10.1007\/BF00291154"},{"key":"2025101801062489000_39.3.162.113","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1159\/000154089","volume":"42","year":"1992","journal-title":"Hum Hered"},{"key":"2025101801062489000_39.3.162.114","first-page":"741","volume":"51","year":"1992","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.115","first-page":"103","volume":"59","year":"1996","journal-title":"Am J Hum Genet"},{"key":"2025101801062489000_39.3.162.116","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.35.8.668"},{"key":"2025101801062489000_39.3.162.117","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1399-0004.1992.tb03226.x","volume":"42","year":"1992","journal-title":"Clin Genet"},{"key":"2025101801062489000_39.3.162.118","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1212\/WNL.45.4.677","volume":"45","year":"1995","journal-title":"Neurology"},{"key":"2025101801062489000_39.3.162.119","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960202)61:4<356::AID-AJMG10>3.0.CO;2-R"},{"key":"2025101801062489000_39.3.162.120","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1007\/BF02267075","volume":"97","year":"1996","journal-title":"Hum Genet"},{"key":"2025101801062489000_39.3.162.121","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1182\/blood.V83.10.2899.2899","volume":"83","year":"1994","journal-title":"Blood"},{"key":"2025101801062489000_39.3.162.122","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000382"},{"key":"2025101801062489000_39.3.162.123","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1987.01060050083043"},{"key":"2025101801062489000_39.3.162.124","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1993.01090110057023"},{"key":"2025101801062489000_39.3.162.125","first-page":"956","volume":"116","year":"1998","journal-title":"Arch Ophthalmol"},{"key":"2025101801062489000_39.3.162.126","doi-asserted-by":"crossref","first-page":"122","DOI":"10.3341\/kjo.1996.10.2.122","volume":"10","year":"1996","journal-title":"Korean J Ophthalmol"},{"key":"2025101801062489000_39.3.162.127","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1136\/bjo.83.5.577","volume":"83","year":"1999","journal-title":"Br J Ophthalmol"},{"key":"2025101801062489000_39.3.162.128","first-page":"15","volume":"12","year":"1992","journal-title":"J Clin Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.129","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1993.01090110048021"},{"key":"2025101801062489000_39.3.162.130","first-page":"163","volume":"14","year":"1994","journal-title":"J Neuroophthalmol"},{"key":"2025101801062489000_39.3.162.131","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00716-9"},{"key":"2025101801062489000_39.3.162.132","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9394(00)00603-6"},{"key":"2025101801062489000_39.3.162.133","doi-asserted-by":"publisher","DOI":"10.1097\/00041327-200020030-00006"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.39.3.162","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T08:06:39Z","timestamp":1760774799000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.39.3.162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,3]]},"references-count":133,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2002,3,1]]},"published-print":{"date-parts":[[2002,3]]}},"alternative-id":["10.1136\/jmg.39.3.162"],"URL":"https:\/\/doi.org\/10.1136\/jmg.39.3.162","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,3]]}}}