ArticleAmerican journal of human genetics2018
Missense Variants in RHOBTB2 Cause a Developmental and Epileptic Encephalopathy in Humans, and Altered Levels Cause Neurological Defects in Drosophila.
Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Genetic Neonatal-Onset Epilepsies and Developmental/Epileptic Encephalopathies with Movement Disorders: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Review
- De novo variants in LDB1 are linked to distinct neurodevelopmental phenotypes determined by variant location and differing pathomechanisms.American journal of human genetics · 2026Article
- Review
- Movement Disorders in Developmental and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Genetic Diagnosis and Discovery Enabled by Large Language Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Alternating Hemispheric Diffusion-Weighted Imaging Abnormalities: A Characteristic Imaging Pattern in RHOBTB2 Encephalopathy.Korean journal of radiology · 2026Article
- Abrupt and Severe Onset of Dystonia, Chorea and Hemiplegic Episodes in a Young Boy with a Novel Heterozygous Missense Variant in the GTPase Domain of RHOBTB2.Movement disorders clinical practice · 2025Article
- Proteasomal activation ameliorates neuronal phenotypes linked to FBXO11-deficiency.HGG advances · 2025Article
- Deregulated ion channels contribute to RHOBTB2-associated developmental and epileptic encephalopathy.Human molecular genetics · 2025Article
- Developmental and Epileptic Encephalopathy: Pathogenesis of Intellectual Disability Beyond Channelopathies.Biomolecules · 2025Review
- RHOBTB2 Variant p.Arg511Gln Causes Developmental and Epileptic Encephalopathy Type 64 in an Infant: A Case Report and Hotspot Variant Analysis.Molecular genetics & genomic medicine · 2025Article
- RAPIDASH: Tag-free enrichment of ribosome-associated proteins reveals composition dynamics in embryonic tissue, cancer cells, and macrophages.Molecular cell · 2024Article
- Characterization of 13 Novel Genetic Variants in Genes Associated with Epilepsy: Implications for Targeted Therapeutic Strategies.Molecular diagnosis & therapy · 2024Article
- Gnao1 is a molecular switch that regulates the Rho signaling pathway in differentiating neurons.Scientific reports · 2024Article
- Long-term effectiveness and tolerability of ketogenic diet therapy in patients with genetic developmental and epileptic encephalopathy onset within the first 6 months of life.Epilepsia open · 2024Article
- Variants inFrontiers in pediatrics · 2024Review
- RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages.bioRxiv : the preprint server for biology · 2023Article
- Multidisciplinary molecular consultation increases the diagnosis of pediatric epileptic encephalopathy and neurodevelopmental disorders.Molecular genetics & genomic medicine · 2023Article
- Genotype-phenotype correlations in RHOBTB2-associated neurodevelopmental disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
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Authors and funding
29 authors at 13 institutions in 6 countries.
Funding
Abstract
Although the role of typical Rho GTPases and other Rho-linked proteins in synaptic plasticity and cognitive function and dysfunction is widely acknowledged, the role of atypical Rho GTPases (such as RHOBTB2) in neurodevelopment has barely been characterized. We have now identified de novo missense variants clustering in the BTB-domain-encoding region of RHOBTB2 in ten individuals with a similar phenotype, including early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorders. Three of the variants were recurrent. Upon transfection of HEK293 cells, we found that mutant RHOBTB2 was more abundant than the wild-type, most likely because of impaired degradation in the proteasome. Similarly, elevated amounts of the Drosophila ortholog RhoBTB in vivo were associated with seizure susceptibility and severe locomotor defects. Knockdown of RhoBTB in the Drosophila dendritic arborization neurons resulted in a decreased number of dendrites, thus suggesting a role of RhoBTB in dendritic development. We have established missense variants in the BTB-domain-encoding region of RHOBTB2 as causative for a developmental and epileptic encephalopathy and have elucidated the role of atypical Rho GTPase RhoBTB in Drosophila neurological function and possibly dendrite development.
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