ArticleBrain : a journal of neurology2024
Digenic Leigh syndrome on the background of the m.11778G>A Leber hereditary optic neuropathy variant.
Article in Brain : a journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 2 of them syntheses that pooled it.
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Who cites it
10 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.
- Clinical spectrum, treatment and outcomes of the m.10197G>A mutation in MT-ND3: a case report, systematic review and meta-analysis.Orphanet journal of rare diseases · 2025Pooled it
- A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum.Diagnostics (Basel, Switzerland) · 2024Guideline
- Identification of Nuclear Genetic Loci Linked to Clinical Features of the m.3243A>G Mitochondrial DNA Variant.Neurology. Genetics · 2026Article
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Recessive variants in mitochondrial complex I nuclear subunits are an underrated cause of optic atrophy.Brain : a journal of neurology · 2026Article
- When LHON Mimics Demyelination: Area Postrema Syndrome in BiallelicJournal of clinical medicine · 2026Article
- RNA Sequencing Resolves Cryptic Pathogenic Variants in Mitochondrial Disease.Annals of clinical and translational neurology · 2026Article
- Modifier variants in metabolic pathways are associated with an increased penetrance of Leber's Hereditary Optic Neuropathy.European journal of human genetics : EJHG · 2026Article
- Identification of co-segregatingFrontiers in medicine · 2025Article
- Digenic Inheritance in Rare Disorders and Mitochondrial Disease-Crossing the Frontier to a More Comprehensive Understanding of Etiology.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
24 authors at 16 institutions in 8 countries.
Funding
Abstract
Leigh syndrome spectrum (LSS) is a primary mitochondrial disorder defined neuropathologically by a subacute necrotizing encephalomyelopathy and characterized by bilateral basal ganglia and/or brainstem lesions. LSS is associated with variants in several mitochondrial DNA genes and more than 100 nuclear genes, most often related to mitochondrial complex I (CI) dysfunction. Rarely, LSS has been reported in association with primary Leber hereditary optic neuropathy (LHON) variants of the mitochondrial DNA, coding for CI subunits (m.3460G>A in MT-ND1, m.11778G>A in MT-ND4 and m.14484T>C in MT-ND6). The underlying mechanism by which these variants manifest as LSS, a severe neurodegenerative disease, as opposed to the LHON phenotype of isolated optic neuropathy, remains an open question. Here, we analyse the exome sequencing of six probands with LSS carrying primary LHON variants, and report digenic co-occurrence of the m.11778G > A variant with damaging heterozygous variants in nuclear disease genes encoding CI subunits as a plausible explanation. Our findings suggest a digenic mechanism of disease for m.11778G>A-associated LSS, consistent with recent reports of digenic disease in individuals manifesting with LSS due to biallelic variants in the recessive LHON-associated disease gene DNAJC30 in combination with heterozygous variants in CI subunits.
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Registered trials
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