ArticleThe Journal of clinical investigation2021
Impaired complex I repair causes recessive Leber's hereditary optic neuropathy.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05554835 (Global Mitochondrial Registry to Define Natural History and Outcome Measures to Achieve Definite Trial Readiness for Mitochondrial Disorders), which is not on this map. Cited by 91 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Global Mitochondrial Registry to Define Natural History and Outcome Measures to Achieve Definite Trial Readiness for Mitochondrial Disorders
Who cites it
91 citing papers in PubMed.
- When LHON Mimics Demyelination: Area Postrema Syndrome in BiallelicJournal of clinical medicine · 2026Article
- Recessive variants in mitochondrial complex I nuclear subunits are an underrated cause of optic atrophy.Brain : a journal of neurology · 2026Article
- Mass spectrometry proteomics for studying mitostasis.Protein science : a publication of the Protein Society · 2026Review
- The m.14484T>C MT-ND6 Mutation Presenting with a Hereditary Spastic-Paraparesis Phenotype.Movement disorders clinical practice · 2026Article
- Functions of J-domain proteins in mitochondrial protein biogenesis.Protein science : a publication of the Protein Society · 2026Review
- Optimized ND4 allotopic expression for gene therapy of Leber's hereditary optic neuropathy.Frontiers in bioengineering and biotechnology · 2026Article
- Genetic Spectrum of Negative Electroretinograms in a Predominantly Pediatric Cohort of 177 Patients.Investigative ophthalmology & visual science · 2025Article
- Article
- Sex Distributions in the Most Frequent Autosomal Genetic Causes of Retinitis Pigmentosa.Investigative ophthalmology & visual science · 2025Article
- Evaluation of Visual and Optical Coherence Tomography Outcomes in Patients with Leber's Hereditary Optic Neuropathy Treated with Idebenone.Life (Basel, Switzerland) · 2025Article
- Biallelic NSUN3 Variants Cause Diverse Phenotypic Spectrum Disease: From Isolated Optic Atrophy to Severe Early-Onset Mitochondrial Disorder.Investigative ophthalmology & visual science · 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
- Clinical and genetic landscape of optic atrophy in 826 families: insights from 50 nuclear genes.Brain : a journal of neurology · 2025Article
- Isolated and Syndromic Genetic Optic Neuropathies: A Review of Genetic and Phenotypic Heterogeneity.International journal of molecular sciences · 2025Review
- Leber's hereditary optic neuropathy - current status of idebenone and gene replacement therapies.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- Article
- Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment.Investigative ophthalmology & visual science · 2025Article
- Leber's Hereditary Optic Neuropathy.Medical archives (Sarajevo, Bosnia and Herzegovina) · 2025Article
- Extraocular features of Leber hereditary optic neuropathy: A scoping review.Journal of biological methods · 2025Review
31 more citing papers are in PubMed but not listed here.
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54 authors.
Funding
Abstract
Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit-encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits.
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