ArticlePloS one2012
Rare primary mitochondrial DNA mutations and probable synergistic variants in Leber's hereditary optic neuropathy.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Pooled it
- Pooled it
- [Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2026Review
- A multistage cost-effective strategy for the molecular diagnosis of unexplained vision loss patients: practice in inherited ocular fundus disease.Molecular genetics and genomics : MGG · 2026Article
- Leber's Hereditary Optic Neuropathy from a Rare Variant, m.3700 G > A, in the MT-ND1 Gene in a Family.Neuro-ophthalmology (Aeolus Press) · 2026Article
- Trans-generational maintenance of mitochondrial DNA integrity in oocytes during early folliculogenesis.PLoS genetics · 2025Article
- Evaluation of Visual and Optical Coherence Tomography Outcomes in Patients with Leber's Hereditary Optic Neuropathy Treated with Idebenone.Life (Basel, Switzerland) · 2025Article
- The crossroads of Leber hereditary optic neuropathy and autosomal dominant optic Atrophy: Clinical profiles of patients with coexisting pathogenic genetic variants.American journal of ophthalmology case reports · 2025Article
- Isolated and Syndromic Genetic Optic Neuropathies: A Review of Genetic and Phenotypic Heterogeneity.International journal of molecular sciences · 2025Review
- Review
- Early Macular Ganglion Cell Loss in Leber Hereditary Optic Neuropathy, an Optical Coherence Tomography Biomarker to Differentiate Optic Neuritis.Journal of clinical medicine · 2025Article
- Adult Leigh Syndrome Associated with the m.15635T>C Mitochondrial DNA Variant Affecting the CytochromeInternational journal of molecular sciences · 2025Article
- Article
- Leber's hereditary optic neuropathy and multiple sclerosis: overlap between mitochondrial disease and neuroinflammation.Frontiers in neurology · 2025Review
- IT TAKES TWO TO TANGO: potential novel therapies for autosomal dominant optic atrophy.Frontiers in ophthalmology · 2025Review
- Leber's Hereditary Optic Neuropathy.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2025Article
- Adult-Onset Bilateral Optic Neuropathy in a Patient with Non-Familial Childhood-Onset Generalized Dystonia Associated with Mitochondrial DNA 14459G>A Mutation: A Case Report and Review of Literature.Neuro-ophthalmology (Aeolus Press) · 2025Article
- Mitochondrial complex I subunitHeliyon · 2024Review
- Identification and characterization of a new pathologic mutation in a large Leber hereditary optic neuropathy pedigree.Orphanet journal of rare diseases · 2024Article
- Efficacy of Intravitreal rAAV2-ND4 Injection in Treated Versus Fellow Eyes with Leber's Hereditary Optic Neuropathy: A Meta-Analysis.Neuro-ophthalmology (Aeolus Press) · 2024Review
Corrections and comments
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Authors and funding
26 authors at 13 institutions in 3 countries.
Funding
Abstract
backgroundLeber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes). However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined. METHODOLOGY/PRINCIPAL
findingsIn order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M), MT-ND4L (m.10663T>C/p.V65A) and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S). Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe) and other putative synergistic mtDNA variants in LHON expression.
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Registered trials
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