ArticleAnnals of neurology2023
Expert Panel Curation of 113 Primary Mitochondrial Disease Genes for the Leigh Syndrome Spectrum.
Article in Annals of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- A Comprehensive Approach to the Diagnosis of Leigh Syndrome Spectrum.Diagnostics (Basel, Switzerland) · 2024Guideline
- A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Advances in diagnosis of mitochondrial dysfunction and primary mitochondrial disease.Disease models & mechanisms · 2026Review
- Advances in Primary Mitochondrial Diseases: Diagnosis, Natural History Studies and Clinical Trials.Genes · 2026Review
- Article
- Identification of novel NDUFA3 variants in a patient with mitochondrial disorders.Pediatric research · 2026Article
- Clinical Spectrum, Heteroplasmy-Phenotype Correlation, and Prognosis of the MT-ND3 m.10191 T > C Mutation.CNS neuroscience & therapeutics · 2026Article
- Accelerating Leigh syndrome drug discovery through deep learning screening in brain organoids.Nature communications · 2026Article
- Diagnosis of pediatric mitochondrial diseases via targeted next-generation sequencing (NGS): real-world data with the Blueprint GeneticsOrphanet journal of rare diseases · 2026Observational
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Characterization of aMolecular genetics and metabolism reports · 2026Article
- Article
- Impaired Complex I dysregulates neural/glial precursors and corpus callosum development revealing postnatal defects in Leigh syndrome mice.EMBO molecular medicine · 2026Article
- Germline variants in ATM, BRCA2, other cancer predisposition and novel candidate genes are implicated in glioma risk in adult glioma patients with a familial or personal history of tumors.Acta neuropathologica · 2026Article
- Pleiotropic effects of MORC2 derive from its epigenetic signature.Brain : a journal of neurology · 2026Article
- Imaging patterns of paediatric CNS mitochondrial disorders.Neuroradiology · 2026Review
- Expanding research and care for Leigh syndrome: efforts of a patient-led advocacy organization.Research involvement and engagement · 2025Article
- Tissue-Specific Regulation of Fatty Acid Metabolism in a Mouse Model of Isolated Complex I Deficiency.Proteomics · 2025Article
- Endocrine Dysfunction in Primary Mitochondrial Diseases.Endocrine reviews · 2025Review
- Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
objectivePrimary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.
methodsThe Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP standardized gene curation for LSS by refining the phenotypic definition, modifying the ClinGen Gene-Disease Clinical Validity Curation Framework to improve interpretation for LSS, and establishing a scoring rubric for LSS.
resultsThe GDR with LSS across the nuclear and mitochondrial genomes was classified as definitive for 31 of 114 GDRs curated (27%), moderate for 38 (33%), limited for 43 (38%), and disputed for 2 (2%). Ninety genes were associated with autosomal recessive inheritance, 16 were maternally inherited, 5 were autosomal dominant, and 3 were X-linked.
interpretationGDRs for LSS were established for genes across both nuclear and mitochondrial genomes. Establishing these GDRs will allow accurate variant interpretation, expedite genetic diagnosis of LSS, and facilitate precision medicine, multisystem organ surveillance, recurrence risk counseling, reproductive choice, natural history studies, and determination of eligibility for interventional clinical trials. ANN NEUROL 2023;94:696-712.
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