ArticleBrain : a journal of neurology2023
Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.
Article in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 29 papers.
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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.
Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network
Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
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- A Case of Monozygotic Twins Carrying a Novel Loss-of-Function Variant in the MYCBP2 Gene, Presenting With Microcephaly, Ectopic Kidney and Growth Restriction.Prenatal diagnosis · 2026Article
- Maternal sleep deprivation reshapes offspring hippocampal development through a Trem2-centered microglial program revealed by single-nucleus and spatial transcriptomics.Molecular psychiatry · 2026Article
- First report of an inherited MYCBP2 neurodevelopmental disorder: review of proband and parent presentation.Neurogenetics · 2026Review
- Tau-induced increase in promoter-proximal RNA polymerase II pausing is linked to suppressed expression of long neuronal genes in aFrontiers in aging neuroscience · 2026Article
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- E3 ubiquitin ligases in signaling, disease, and therapeutics.Trends in biochemical sciences · 2025Review
- Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling.American journal of human genetics · 2025Article
- Ubiquitin ligase signalling networks shape presynaptic development, function and disease.The Journal of physiology · 2025Review
- Axon termination of the SAB motor neurons inbioRxiv : the preprint server for biology · 2025Article
- Pathogenic variants inmedRxiv : the preprint server for health sciences · 2025Article
- Rest Induces a Distinct Transcriptional Program in the Nervous System of the ExercisedInternational journal of molecular sciences · 2025Article
- MYCBP2-mediated HNF4α ubiquitination reprogrammed lipid metabolism in MASH-associated hepatocellular carcinoma.Oncogene · 2025Article
- First Report of a FamiliarBalkan journal of medical genetics : BJMG · 2025Article
- Unique signatures of highly constrained genes across publicly available genomic databases.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- Multimodal MRI-based radiomics in an ASD rat model: investigating brain structural changes and the neuroprotective effects of selenium.Frontiers in neuroscience · 2025Article
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Article
- Integrin adhesome axis inhibits the RPM-1 ubiquitin ligase signaling hub to regulate growth cone and axon development.PLoS genetics · 2024Article
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Authors and funding
28 authors at 13 institutions in 4 countries.
Funding
Abstract
The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured a distinct de novo variant in MYCBP2, a gene encoding an atypical really interesting new gene (RING) ubiquitin ligase and signalling hub with evolutionarily conserved functions in axon development. We used CRISPR/Cas9 gene editing to introduce disease-associated variants into conserved residues in the Caenorhabditis elegans MYCBP2 orthologue, RPM-1, and evaluated functional outcomes in vivo. Consistent with variable phenotypes in patients with MYCBP2 variants, C. elegans carrying the corresponding human mutations in rpm-1 displayed axonal and behavioural abnormalities including altered habituation. Furthermore, abnormal axonal accumulation of the autophagy marker LGG-1/LC3 occurred in variants that affect RPM-1 ubiquitin ligase activity. Functional genetic outcomes from anatomical, cell biological and behavioural readouts indicate that MYCBP2 variants are likely to result in loss of function. Collectively, our results from multiple human patients and CRISPR gene editing with an in vivo animal model support a direct link between MYCBP2 and a human neurodevelopmental spectrum disorder that we term, MYCBP2-related developmental delay with corpus callosum defects (MDCD).
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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.