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Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis
Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes loss of central vision. Three primary variants (m.3460G>A, m.11778G>A, and m.14484T>C) and about 16 secondary variants are responsible for LHON in the majority of the cases. We investigated the complete mitoc...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472268/ https://www.ncbi.nlm.nih.gov/pubmed/34573281 http://dx.doi.org/10.3390/genes12091300 |
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author | Jha, Rajan Kumar Dawar, Chhavi Hasan, Qurratulain Pujar, Akhilesh Gupta, Gaurav Vishnu, Venugopalan Y. Kekunnaya, Ramesh Thangaraj, Kumarasamy |
author_facet | Jha, Rajan Kumar Dawar, Chhavi Hasan, Qurratulain Pujar, Akhilesh Gupta, Gaurav Vishnu, Venugopalan Y. Kekunnaya, Ramesh Thangaraj, Kumarasamy |
author_sort | Jha, Rajan Kumar |
collection | PubMed |
description | Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes loss of central vision. Three primary variants (m.3460G>A, m.11778G>A, and m.14484T>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>A and m.14484T>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>C and m.13708G>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. |
format | Online Article Text |
id | pubmed-8472268 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84722682021-09-28 Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis Jha, Rajan Kumar Dawar, Chhavi Hasan, Qurratulain Pujar, Akhilesh Gupta, Gaurav Vishnu, Venugopalan Y. Kekunnaya, Ramesh Thangaraj, Kumarasamy Genes (Basel) Article Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disorder that causes loss of central vision. Three primary variants (m.3460G>A, m.11778G>A, and m.14484T>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>A and m.14484T>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>C and m.13708G>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. MDPI 2021-08-24 /pmc/articles/PMC8472268/ /pubmed/34573281 http://dx.doi.org/10.3390/genes12091300 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jha, Rajan Kumar Dawar, Chhavi Hasan, Qurratulain Pujar, Akhilesh Gupta, Gaurav Vishnu, Venugopalan Y. Kekunnaya, Ramesh Thangaraj, Kumarasamy Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis |
title | Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis |
title_full | Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis |
title_fullStr | Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis |
title_full_unstemmed | Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis |
title_short | Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis |
title_sort | mitochondrial genetic heterogeneity in leber’s hereditary optic neuropathy: original study with meta-analysis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472268/ https://www.ncbi.nlm.nih.gov/pubmed/34573281 http://dx.doi.org/10.3390/genes12091300 |
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