{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:50:13Z","timestamp":1791607813124,"version":"4.3.4"},"reference-count":75,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Leber\u2019s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes loss of central vision. Three primary variants (m.3460G&gt;A, m.11778G&gt;A, and m.14484T&gt;C) and about 16 secondary variants are responsible for LHON in the majority of the cases. We investigated the complete mitochondrial DNA (mtDNA) sequences of 189 LHON patients and found a total of 54 disease-linked pathogenic variants. The primary variants m.11778G&gt;A and m.14484T&gt;C were accountable for only 14.81% and 2.64% cases, respectively. Patients with these two variants also possessed additional disease-associated variants. Among 156 patients who lacked the three primary variants, 16.02% harboured other LHON-associated variants either alone or in combination with other disease-associated variants. Furthermore, we observed that none of the haplogroups were explicitly associated with LHON. We performed a meta-analysis of m.4216T&gt;C and m.13708G&gt;A and found a significant association of these two variants with the LHON phenotype. Based on this study, we recommend the use of complete mtDNA sequencing to diagnose LHON, as we found disease-associated variants throughout the mitochondrial genome.<\/jats:p>","DOI":"10.3390\/genes12091300","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T22:12:22Z","timestamp":1629843142000},"page":"1300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mitochondrial Genetic Heterogeneity in Leber\u2019s Hereditary Optic Neuropathy: Original Study with Meta-Analysis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-7001","authenticated-orcid":false,"given":"Rajan Kumar","family":"Jha","sequence":"first","affiliation":[{"name":"CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chhavi","family":"Dawar","sequence":"additional","affiliation":[{"name":"CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, India"},{"name":"Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qurratulain","family":"Hasan","sequence":"additional","affiliation":[{"name":"Kamineni Hospital, L.B. Nagar, Hyderabad 500068, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhilesh","family":"Pujar","sequence":"additional","affiliation":[{"name":"Child Sight Institute, L V Prasad Eye Institute (LVPEI), Hyderabad 500034, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2944-9074","authenticated-orcid":false,"given":"Gaurav","family":"Gupta","sequence":"additional","affiliation":[{"name":"Genome Foundation, Hyderabad 500034, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3654-8137","authenticated-orcid":false,"given":"Venugopalan Y.","family":"Vishnu","sequence":"additional","affiliation":[{"name":"All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5789-2300","authenticated-orcid":false,"given":"Ramesh","family":"Kekunnaya","sequence":"additional","affiliation":[{"name":"Child Sight Institute, L V Prasad Eye Institute (LVPEI), Hyderabad 500034, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumarasamy","family":"Thangaraj","sequence":"additional","affiliation":[{"name":"CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, India"},{"name":"Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500039, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"ref_1","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":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.mrfmmm.2008.06.004","article-title":"Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A","volume":"643","author":"Wang","year":"2008","journal-title":"Mutat. 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