ArticleEMBO molecular medicine2020
Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome and stalled biogenesis of complex I.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Proteomic Characterization of Replication Stress and Impaired Antioxidant Defense in Tacrolimus-Induced Chronic Nephrotoxicity.International journal of molecular sciences · 2026Article
- Mitochondrial complex I deficiency-associated diseases and models.Cellular and molecular life sciences : CMLS · 2026Review
- Multi-omics Analysis of Energy Metabolism Pathways Across Major Psychiatric Disorders.Molecular neurobiology · 2025Article
- Bi-allelic variants in MRPL49 cause variable clinical presentations, including sensorineural hearing loss, leukodystrophy, and ovarian insufficiency.American journal of human genetics · 2025Article
- Review: Utility of mass spectrometry in rare disease research and diagnosis.NPJ genomic medicine · 2025Review
- COA5 has an essential role in the early stage of mitochondrial complex IV assembly.Life science alliance · 2025Article
- Mitochondrial complex-1 as a therapeutic target for cardiac diseases.Molecular and cellular biochemistry · 2025Review
- Epigenetic regulation of the respiratory chain by a mitochondrial distress-related redox signal.Frontiers in cell and developmental biology · 2025Article
- Leigh Syndrome due toMolecular syndromology · 2024Article
- Variants in ATP5F1B are associated with dominantly inherited dystonia.Brain : a journal of neurology · 2023Article
- An Overview of Mitochondrial Protein Defects in Neuromuscular Diseases.Biomolecules · 2021Review
- Tackling Dysfunction of Mitochondrial Bioenergetics in the Brain.International journal of molecular sciences · 2021Review
- Complexome Profiling: Assembly and Remodeling of Protein Complexes.International journal of molecular sciences · 2021Review
- The genetics of mitochondrial disease: dissecting mitochondrial pathology using multi-omic pipelines.The Journal of pathology · 2021Review
- Mitochondrial Structure and Bioenergetics in Normal and Disease Conditions.International journal of molecular sciences · 2021Review
- Complexome Profiling-Exploring Mitochondrial Protein Complexes in Health and Disease.Frontiers in cell and developmental biology · 2021Review
- Analysis of Human Mutations in the Supernumerary Subunits of Complex I.Life (Basel, Switzerland) · 2020Review
- Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome and stalled biogenesis of complex I.EMBO molecular medicine · 2020Article
- Complex I deficiency and Leigh syndrome through the eyes of a clinician.EMBO molecular medicine · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
Leigh syndrome is a progressive neurodegenerative disorder, most commonly observed in paediatric mitochondrial disease, and is often associated with pathogenic variants in complex I structural subunits or assembly factors resulting in isolated respiratory chain complex I deficiency. Clinical heterogeneity has been reported, but key diagnostic findings are developmental regression, elevated lactate and characteristic neuroimaging abnormalities. Here, we describe three affected children from two unrelated families who presented with Leigh syndrome due to homozygous variants (c.346_*7del and c.173A>T p.His58Leu) in NDUFC2, encoding a complex I subunit. Biochemical and functional investigation of subjects' fibroblasts confirmed a severe defect in complex I activity, subunit expression and assembly. Lentiviral transduction of subjects' fibroblasts with wild-type NDUFC2 cDNA increased complex I assembly supporting the association of the identified NDUFC2 variants with mitochondrial pathology. Complexome profiling confirmed a loss of NDUFC2 and defective complex I assembly, revealing aberrant assembly intermediates suggestive of stalled biogenesis of the complex I holoenzyme and indicating a crucial role for NDUFC2 in the assembly of the membrane arm of complex I, particularly the ND2 module.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.