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...
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2021-08-01
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| author | Rajan Kumar Jha Chhavi Dawar Qurratulain Hasan Akhilesh Pujar Gaurav Gupta Venugopalan Y. Vishnu Ramesh Kekunnaya Kumarasamy Thangaraj |
| author_facet | Rajan Kumar Jha Chhavi Dawar Qurratulain Hasan Akhilesh Pujar Gaurav Gupta Venugopalan Y. Vishnu Ramesh Kekunnaya Kumarasamy Thangaraj |
| author_sort | Rajan Kumar Jha |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T07:38:36Z |
| format | Article |
| id | doaj.art-562c58daf40b4adbbba2925e455a3ab7 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T07:38:36Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-562c58daf40b4adbbba2925e455a3ab72023-11-22T13:12:53ZengMDPI AGGenes2073-44252021-08-01129130010.3390/genes12091300Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-AnalysisRajan Kumar Jha0Chhavi Dawar1Qurratulain Hasan2Akhilesh Pujar3Gaurav Gupta4Venugopalan Y. Vishnu5Ramesh Kekunnaya6Kumarasamy Thangaraj7CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, IndiaCSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, IndiaKamineni Hospital, L.B. Nagar, Hyderabad 500068, IndiaChild Sight Institute, L V Prasad Eye Institute (LVPEI), Hyderabad 500034, IndiaGenome Foundation, Hyderabad 500034, IndiaAll India Institute of Medical Sciences, New Delhi 110029, IndiaChild Sight Institute, L V Prasad Eye Institute (LVPEI), Hyderabad 500034, IndiaCSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad 500007, IndiaLeber’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.https://www.mdpi.com/2073-4425/12/9/1300LHONmtDNAmeta-analysishaplogroupprimary variantsDNA sequencing |
| spellingShingle | Rajan Kumar Jha Chhavi Dawar Qurratulain Hasan Akhilesh Pujar Gaurav Gupta Venugopalan Y. Vishnu Ramesh Kekunnaya Kumarasamy Thangaraj Mitochondrial Genetic Heterogeneity in Leber’s Hereditary Optic Neuropathy: Original Study with Meta-Analysis Genes LHON mtDNA meta-analysis haplogroup primary variants DNA sequencing |
| 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 | LHON mtDNA meta-analysis haplogroup primary variants DNA sequencing |
| url | https://www.mdpi.com/2073-4425/12/9/1300 |
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