Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2021 Aug 24;12(9):1300.
doi: 10.3390/genes12091300.

Mitochondrial Genetic Heterogeneity in Leber's Hereditary Optic Neuropathy: Original Study with Meta-Analysis

Rajan Kumar Jha  1 , Chhavi Dawar  1   2 , Qurratulain Hasan  3 , Akhilesh Pujar  4 , Gaurav Gupta  5 , Venugopalan Y Vishnu  6 , Ramesh Kekunnaya  4 , Kumarasamy Thangaraj  1   7
Affiliations
Meta-Analysis

Mitochondrial Genetic Heterogeneity in Leber's Hereditary Optic Neuropathy: Original Study with Meta-Analysis

Rajan Kumar Jha et al. Genes (Basel). .

Abstract

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.

Keywords: DNA sequencing; LHON; haplogroup; meta-analysis; mtDNA; primary variants.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
World map showing frequency of primary LHON variants. (A) Frequency of m.3460G>A, (B) m.11778G>A, and (C) m.14484T>C variants. The black dots represent the regions from which samples were included in the publication.
Figure 2
Figure 2
Forest plot showing odds ratios (ORs) for individual studies and pooled odds ratio (OR) using both fixed- and random-effect models of meta-analysis for (A) m.4216T>C variant and (B) m.13708G>A variant.
Figure 3
Figure 3
Funnel plot representing publication bias in the studies involving (A) m.4216T>C variant and (B) m.13708G>A variant.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wallace D.C., Singh G., Lott M.T., Hodge J.A., Schurr T.G., Lezza A.M.S., Elsas L.J., Nikoskelainen E.K. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 1988;242:1427–1430. doi: 10.1126/science.3201231. - DOI - PubMed
    1. Wang H.W., Jia X., Ji Y., Kong Q.P., Zhang Q., Yao Y.G., Zhang Y.P. Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A. Mutat. Res.-Fundam. Mol. Mech. Mutagen. 2008;643:48–53. doi: 10.1016/j.mrfmmm.2008.06.004. - DOI - PubMed
    1. Man P.Y.W., Griffiths P.G., Brown D.T., Howell N., Turnbull D.M., Chinnery P.F. The epidemiology of leber hereditary optic neuropathy in the North East of England. Am. J. Hum. Genet. 2003;72:333–339. doi: 10.1086/346066. - DOI - PMC - PubMed
    1. Man P.Y.W., Turnbull D.M., Chinnery P.F. Leber hereditary optic neuropathy Topic collections Leber hereditary optic neuropathy. J. Med. Genet. 2002;3939:162–169. doi: 10.1136/jmg.39.3.162. - DOI - PMC - PubMed
    1. Carelli V., Ross-Cisneros F.N., Sadun A.A. Mitochondrial dysfunction as a cause of optic neuropathies. Prog. Retin. Eye Res. 2004;23:53–89. doi: 10.1016/j.preteyeres.2003.10.003. - DOI - PubMed

Publication types

Substances

LinkOut - more resources