ArticleNature communications2020
Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.
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In one paragraph
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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36citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 4% of its field
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 53 citations in OpenAlex.
- Proteome-wide Mendelian randomization identifies causal plasma proteins in frontotemporal dementia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Clinical insights into dental care for siblings with Jamuar syndrome: a rare genetic dual case report.European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry · 2026Article
- Gut-Derived Hippuric Acid Alleviates Hepatic Lipid Metabolism via UGDH/FOXK1/CD36 Axis in Obese Mice.Drug design, development and therapy · 2026Article
- Phosphorylation of UDP-glucose dehydrogenase increases glycosaminoglycan biosynthesis and promotes tumor cell motility, spheroid growth, and therapeutic resistance.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Recent insights into the implications of UGDH mutations for human developmental disease.Biochemical Society transactions · 2025Review
- Assessing the diagnostic impact of blood transcriptome profiling in a pediatric cohort previously assessed by genome sequencing.NPJ genomic medicine · 2025Article
- UDP-glucose dehydrogenase variants cause dystroglycanopathy.Annals of clinical and translational neurology · 2025Article
- Regulation of CNS Lipids by Protease Activated Receptor 1.Journal of neurochemistry · 2025Article
- Human skeletal muscle fiber heterogeneity beyond myosin heavy chains.Nature communications · 2025Article
- Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Morphogenetic Designs, and Disease Models in Central Nervous System Organoids.International journal of molecular sciences · 2024Review
- In vitro human cell culture models in a bench-to-bedside approach to epilepsy.Epilepsia open · 2024Review
- Phenotypic and genetic characteristics of 24 cases of early infantile epileptic encephalopathy in East China, including a rare case of biallelic UGDH mutations.Molecular genetics & genomic medicine · 2023Article
- Neurodevelopmental defects in human cortical organoids withScience advances · 2023Article
- Biallelic mutations inGenes & diseases · 2023Article
- UDP-glucuronate metabolism controls RIPK1-driven liver damage in nonalcoholic steatohepatitis.Nature communications · 2023Article
- Copy Number Variations in Children with Tourette Syndrome: Systematic Investigation in a Clinical Setting.Genes · 2023Article
- Toward the use of novel alternative methods in epilepsy modeling and drug discovery.Frontiers in neurology · 2023Review
- Case report: A founder UGDH variant associated with developmental epileptic encephalopathy in Saudi Arabia.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
85 authors at 20 institutions in 12 countries.
Holger Hengel *Department of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.ORCID http://orcid.org/0000-0002-9773-2667
Célia Bosso-Lefèvre *Institute of Medical Biology, A*STAR, Biopolis, Singapore, 138648, Singapore.
George GradyDepartment of Molecular and Structural Biochemistry North Carolina State University, Raleigh, NC, 27607, USA.
Emmanuelle Szenker-RaviInstitute of Medical Biology, A*STAR, Biopolis, Singapore, 138648, Singapore.
Hankun LiYale-NUS College, 12 College Avenue West, Biopolis, Singapore, Singapore.
Sarah PierceDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.
Élise LebigotService De Biochimie, Hopital Bicêtre, Assistance publique-Hôpitaux de Paris, 78 avenue du general leclerc, Le Kremlin Bicêtre, France.ORCID http://orcid.org/0000-0003-0419-8547
Thong-Teck TanInstitute of Medical Biology, Singapore Stem Cell Bank, A∗STAR, Biopolis, Singapore, 138648, Singapore.
Michelle Y EioInstitute of Medical Biology, Singapore Stem Cell Bank, A∗STAR, Biopolis, Singapore, 138648, Singapore.
Gunaseelan NarayananInstitute of Medical Biology, Singapore Stem Cell Bank, A∗STAR, Biopolis, Singapore, 138648, Singapore.
Kagistia Hana UtamiTranslational Laboratory in Genetic Medicine, Agency for Science, Technology, and Research, Singapore (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore, 138648, Singapore.
Monica YauProgram in Developmental & Stem Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics, The University of Toronto, Toronto, ON, Canada.
Nader HandalCaritas Baby Hospital Bethlehem, Bethlehem, State of Palestine.
Werner DeigendeschCaritas Baby Hospital Bethlehem, Bethlehem, State of Palestine.
Reinhard KeimerPed Neurology, Staufer Hospital, Wetzgauer Straße 85, Schwäbisch-Gmünd, Germany.
Hiyam M MarzouqaCaritas Baby Hospital Bethlehem, Bethlehem, State of Palestine.
Meral Gunay-AygunMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Michael J MurielloMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
Helene VerhelstDepartment of Paediatric Neurology, Ghent University Hospital, Ghent, Belgium.
Sarah WeckhuysenCenter for Molecular Neurology, VIB, Antwerp, Belgium.
Sonal MahidaDivision of Neurology and Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
Sakkubai NaiduDivision of Neurology and Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
Terrence G ThomasNeurology Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore.
Jiin Ying LimGenetics Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore.
Ee Shien TanGenetics Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore.
Damien HayeService de Génétique Médicale, CHU De Nice Hôpital de l'Archet 2, 151 route Saint Antoine de la Ginestière, CS 23079 062002, Nice, Cedex 3, France.
Michèl A A P WillemsenDepartment of Pediatric Neurology, Radboud University Medical Center, Nijmegen, The Netherlands.
Renske OegemaDepartment of Genetics, University Medical Center Utrecht, Utrecht, The Netherlands.ORCID http://orcid.org/0000-0002-7146-617X
Wendy G MitchellNeurology Division, Childrens Hospital Los Angeles & Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA.
Tyler Mark PiersonDepartment of Pediatrics, Department of Neurology, & the Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1985-3671
Marisa V AndrewsDivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-5448-1204
Marcia C WillingDivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Lance H RodanDivision of Genetics and Genomics and Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
Tahsin Stefan BarakatDepartment of Clinical Genetics, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-1231-1562
Marjon van SlegtenhorstDepartment of Clinical Genetics, Erasmus MC, University Medical Center, Wytemaweg 80, 3015 CN, Rotterdam, The Netherlands.
Ralitza H GavrilovaDepartment of Clinical Genomics, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
Diego MartinelliGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, viale San Paolo 15, 00146, Rome, Italy.
Tal GilboaChild Neurology Unit, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel.ORCID http://orcid.org/0000-0003-3060-422X
Abdullah M TamimPediatric Neurology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Mais O HashemDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Moeenaldeen D AlSayedDepartment of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Maha M AbdulrahimDepartment of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Mohammed Al-OwainDepartment of Medical Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Ali AwajiDepartment of Pediatrics, King Fahad Central Hospital in Jizan, Abu Arish, Saudi Arabia.
Adel A H MahmoudPediatric Neurology Department, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.
Eissa A FaqeihSection of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Ali Al AsmariSection of Medical Genetics, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
Sulwan M AlgainGeneral Pediatrics and Adolescents, King Fahad Medical City, Riyadh, Saudi Arabia.
Lamyaa A JadPediatric Neurology Department, National Neuroscience Institute, King Fahad Medical City, Riyadh, Saudi Arabia.
Hesham M AldhalaanNeuroscience Department King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Ingo HelbigDivision of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8486-0558
David A KoolenDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Angelika RiessInstitute of Medical Genetics and Applied Genomics (Tübingen) and Centogene AG (Rostock), Rostock, Germany.
Ingeborg Kraegeloh-MannDepartment of Pediatric Neurology, University of Tübingen, Tübingen, Germany.
Peter BauerInstitute of Medical Genetics and Applied Genomics (Tübingen) and Centogene AG (Rostock), Rostock, Germany.
Suleyman GulsunerDivision of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3897-1238
Hannah StambergerCenter for Molecular Neurology, VIB, Antwerp, Belgium.
Alvin Yu Jin NgInstitute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore, 138673, Singapore.
Sha TangDivision of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, USA.
Sumanty TohariInstitute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore, 138673, Singapore.
Boris KerenAPHP, GH Pitié Salpêtrière, Department of Genetics, Unit of Development Genomics, Paris, France.
Laura E Schultz-RogersDepartment of Clinical Genomics, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-7222-9985
Eric W KleeDepartment of Clinical Genomics, Mayo Clinic, 200 First Street SW, Rochester, MN, USA.
Sabina BarresiGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, viale San Paolo 15, 00146, Rome, Italy.ORCID http://orcid.org/0000-0002-7307-388X
Marco TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, viale San Paolo 15, 00146, Rome, Italy.
Hagar Mor-ShakedDepartment of Genetic and Metabolic Diseases, Hadassah-Hebrew University Medical Center, 9112001, Jerusalem, Israel.
Sateesh MaddirevulaDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Amber BegtrupGeneDx, 207 Perry Parkway, Gaithersburg, MD, 20877, USA.
Aida TelegrafiGeneDx, 207 Perry Parkway, Gaithersburg, MD, 20877, USA.
Rolph PfundtDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
Rebecca SchüleDepartment of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Brian CirunaProgram in Developmental & Stem Cell Biology, The Hospital for Sick Children, Department of Molecular Genetics, The University of Toronto, Toronto, ON, Canada.
Carine BonnardInstitute of Medical Biology, A*STAR, Biopolis, Singapore, 138648, Singapore.
Mahmoud A PouladiTranslational Laboratory in Genetic Medicine, Agency for Science, Technology, and Research, Singapore (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore, 138648, Singapore.
James C StewartInstitute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore, 138673, Singapore.
Adam Claridge-ChangInstitute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore, 138673, Singapore.
Dirk J LefeberDepartment of Neurology, Donders Center for Brain, Cognition, and Behavior, Nijmegen, The Netherlands.
Fowzan S AlkurayaDepartment of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.ORCID http://orcid.org/0000-0003-4158-341X
Ajay S MathuruYale-NUS College, 12 College Avenue West, Biopolis, Singapore, Singapore.ORCID http://orcid.org/0000-0003-4591-5274
Byrappa VenkateshNational University of Singapore, Department of Paediatrics, Yong Loo Lin School of Medicine, Biopolis, Singapore, Singapore.ORCID http://orcid.org/0000-0003-3620-0277
Joseph J BaryckiDepartment of Molecular and Structural Biochemistry North Carolina State University, Raleigh, NC, 27607, USA.
Melanie A SimpsonDepartment of Molecular and Structural Biochemistry North Carolina State University, Raleigh, NC, 27607, USA.
Saumya S JamuarGenetics Service, Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore.
Ludger SchölsDepartment of Neurology and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. ludger.schoels@uni-tuebingen.de.
Bruno ReversadeInstitute of Medical Biology, A*STAR, Biopolis, Singapore, 138648, Singapore. bruno@reversade.com.ORCID http://orcid.org/0000-0002-4070-7997
Agency for Science, Technology and Research · SGKing Faisal Specialist Hospital & Research Centre · SAKing Fahd Medical City · SARadboud University Nijmegen · NLBambino Gesù Children's Hospital · ITBethlehem University · PSGerman Center for Neurodegenerative Diseases · DEMayo Clinic · USNorth Carolina State University · USCentogene (Germany) · DEErasmus MC · NLHadassah Medical Center · ILJohns Hopkins University · USKennedy Krieger Institute · USSingHealth Duke-NUS Academic Medical Centre · SGUniversity of Antwerp · BEUniversity of Toronto · CAUniversity of Washington Medical Center · USWashington University in St. Louis · USAmbry Genetics (United States) · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.
Indexed as
Genes, RecessiveAdolescentAllelesAnimalsChildChild, PreschoolEpilepsyFemaleHumansInfantKineticsLoss of Function MutationMaleOrganoidsOxidoreductasesPedigreeOxidoreductasesUGDH protein, humanUridine Diphosphate Glucose Dehydrogenase
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