ArticleNeuron2020
Pathogenic DDX3X Mutations Impair RNA Metabolism and Neurogenesis during Fetal Cortical Development.
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Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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128citing papers in PubMed
9.8field-weighted citation impact, top 1% of its field
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128 citing papers in PubMed, 213 citations in OpenAlex.
- Using Solution NMR to Study the RNA-Binding Properties and Molecular Mechanisms of the RNA Helicase DDX3X.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Impact of environmental enrichment and allostatic load induced by repeated mixing on the transcriptome of three porcine brain tissues.Molecular brain · 2026Article
- DDX3x Regulates NINJ1 Transcription via Histone Lactylation in Sepsis Associated-Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Great Escape: A Case Series onThe Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association · 2026Article
- Identification of highly immunogenic endogenous dsRNAs from cellular MDA5 filaments.bioRxiv : the preprint server for biology · 2026Article
- Modeling rare coding variation on chromosome X provides insight into the genetics and differential sex prevalence of autism spectrum disorder.medRxiv : the preprint server for health sciences · 2026Article
- DDX3X Syndrome: Clinical, Neuroimaging, AI-Assisted Facial Profiling and Genotype-Phenotype Correlations.Genes · 2026Observational
- The inactive X chromosome as a female protector in autism and beyond.Nature genetics · 2026Review
- Knockdown of Ddx3x in mPFC induces autistic-like phenotype in mice via altered synaptic plasticity.Translational psychiatry · 2026Article
- The human DEAD-box protein DDX3X regulates host and viral mRNA translation during Sendai Virus infection.bioRxiv : the preprint server for biology · 2026Article
- Med13 is involved in the radial migration and contralateral projection of cortical neurons via PlxnA4.Communications biology · 2026Article
- A novel lncRNA, lncMCL1, modulates neural pyroptosis associated with epilepsy via stabilizing DDX3X.Cell death and differentiation · 2026Article
- Exome Sequencing Resolving a Complex Pediatric Neurodevelopmental Disorder After Inconclusive Prenatal Testing: A Case Report.Children (Basel, Switzerland) · 2026Article
- E3 ubiquitin ligase trim36 targets ddx3x for degradation to reprogram macrophage polarization and ameliorate tubal factor infertility in rats.Cell biology and toxicology · 2026Article
- Evaluation of the contribution of trio-exome sequencing in selected prenatal indications.Frontiers in genetics · 2026Article
- Article
- DDX3X Aggravates Neuronal Pyroptosis and Inhibits Autophagy via NLRP3 Inflammasome After Experimental Subarachnoid Hemorrhage.Molecular neurobiology · 2025Article
- DDX3X acts as a selective dual switch regulator of mRNA translation in acute ER stress.Cell reports · 2025Article
- Effective in vivo RNA base editing via engineered cytidine deaminase APOBECs fused with PUF proteins.Nature communications · 2025Article
- Impaired cortical development and translational control in a missense mouse model of DDX3X syndrome.Disease models & mechanisms · 2025Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
54 authors at 20 institutions in 8 countries.
Ashley L LennoxDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Mariah L HoyeDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Ruiji JiangDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Bethany L Johnson-KernerDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Lindsey A SuitDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Srivats VenkataramananDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94158, USA.
Charles J SheehanDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Fernando C AlsinaDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Brieana FregeauDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Kimberly A AldingerCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Ching MoeyThe University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, Australia.
Iryna LobachDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94158, USA.
Alexandra AfenjarCentre de référence des malformations et maladies congénitales du cervelet et Département de génétique et embryologie médicale, APHP, Sorbonne Université, Hôpital Armand Trousseau, 75012 Paris, France.
Dusica Babovic-VuksanovicDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA; Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Stéphane BézieauService de Génétique Médicale, CHU Nantes, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France.
Patrick R BlackburnDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Jens BuntThe University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, Australia.
Lydie BurglenCentre de référence des malformations et maladies congénitales du cervelet et Département de génétique et embryologie médicale, APHP, Sorbonne Université, Hôpital Armand Trousseau, 75012 Paris, France.
Philippe M CampeauDepartment of Pediatrics, University of Montreal and CHU Sainte-Justine, Montreal, QC, Canada.
Perrine CharlesDépartement de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière et Hôpital Trousseau, APHP, Sorbonne Université, Paris, France.
Brian H Y ChungDepartment of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Benjamin CognéService de Génétique Médicale, CHU Nantes, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France.
Cynthia CurryGenetic Medicine, University of California San Francisco/Fresno, Fresno, CA 93701, USA.
Maria Daniela D'AgostinoDivision of Medical Genetics, Departments of Specialized Medicine and Human Genetics, McGill University, Montreal, QC, Canada.
Nataliya Di DonatoInstitute for Clinical Genetics, TU Dresden, Dresden, Germany.
Laurence FaivreCentre de référence Anomalies du Développement et Syndromes Malformatifs, INSERM UMR 1231 GAD, CHU de Dijon et Université de Bourgogne, Dijon, France.
Delphine HéronAPHP, Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
A Micheil InnesDepartment of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Bertrand IsidorService de Génétique Médicale, CHU Nantes, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France.
Boris KerenAPHP, Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
Amy KimballHarvey Institute of Human Genetics, Greater Baltimore Medical Center, Baltimore, MD, USA.
Eric W KleeDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Paul KuentzUMR-INSERM 1231 GAD, Génétique des Anomalies du développement, Université de Bourgogne Franche-Comté, Dijon, France.
Sébastien KüryService de Génétique Médicale, CHU Nantes, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France.
Dominique Martin-CoignardService de Génétique, Centre hospitalier du Mans, Le Mans, France.
Ghayda MirzaaCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Department of Pediatrics, University of Washington, Seattle, WA 98101, USA.
Cyril MignotDépartement de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière et Hôpital Trousseau, APHP, Sorbonne Université, Paris, France.
Noriko MiyakeDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Atsushi FujitaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
Caroline NavaAPHP, Département de Génétique, Groupe Hospitalier Pitié Salpêtrière, Paris, France.
Mathilde NizonService de Génétique Médicale, CHU Nantes, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France.
Diana RodriguezCentre de Référence Neurogénétique & Service de Neurologie Pédiatrique, APHP, Sorbonne Université, Hôpital Armand Trousseau, 75012 Paris, France.
Lot Snijders BlokDepartment of Human Genetics, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Christel Thauvin-RobinetCentre de référence Déficience Intellectuelle, INSERM UMR 1231 GAD, CHU de Dijon et Université de Bourgogne, Dijon, France.
Julien ThevenonCentre de référence Anomalies du Développement et Syndromes Malformatifs, INSERM UMR 1231 GAD, CHU de Dijon et Université de Bourgogne, Dijon, France.
Marie VincentService de Génétique Médicale, CHU Nantes, 9 quai Moncousu, 44093 Nantes Cedex 1, France; Université de Nantes, CNRS, INSERM, l'institut du thorax, 44000 Nantes, France.
Alban ZieglerService de Génétique, CHU d'Angers, Angers, France.
William DobynsCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA; Departments of Pediatrics and Neurology, University of Washington, Seattle, WA 98101, USA.
Linda J RichardsThe University of Queensland, Queensland Brain Institute, Brisbane, QLD 4072, Australia; The University of Queensland, School of Biomedical Sciences, Brisbane 4072, QLD, Australia.
A James BarkovichDepartment of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94158, USA.
Stephen N FloorDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94158, USA; Helen Diller Family Comprehensive Cancer Center, San Francisco, CA 94158, USA.
Debra L SilverDepartment of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Duke Institute for Brain Sciences, Duke University, Durham, NC 27710, USA. Electronic address: debra.silver@duke.edu.
Elliott H SherrDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA; Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: elliott.sherr@ucsf.edu.
University of California, San Francisco · USSorbonne Université · FRDuke Medical Center · USUniversité de Bourgogne · FRUniversity of Queensland · AUWinnMed · USYokohama City University · JPAssistance Publique – Hôpitaux de Paris · FRCentre National de la Recherche Scientifique · FRInstitut du Thorax · FRUniversity of Washington · USCalifornia State University, Fresno · USCentre Hospitalier du Mans · FRCentre Hospitalier Universitaire d'Angers · FRCentre Hospitalier Universitaire Sainte-Justine · CADuke University Hospital · USGreater Baltimore Medical Center · USInserm · FRMcGill University · CANantes Université · FR
Funding
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6MORGANIZATION AND FUNCTIONS OF CELLULAR STRUCTUREST32GM007184 · NIGMS · DUKE UNIVERSITY · PI JINKS-ROBERTSON, SUE · 1985 to 2019
$18.2MDe novo copy number variation and gene discovery in human brain malformationsR01NS058721 · NINDS · UNIVERSITY OF CHICAGO · PI ARGILLI, EMANUELA · 2008 to 2025
$10.9MThe Genetic Basis of Mid-Hindbrain MalformationsR01NS050375 · NINDS · UNIVERSITY OF MINNESOTA · PI DOBYNS, WILLIAM B. · 2005 to 2019
$9.9MMechanisms of neural progenitor division in the developing brainR01NS083897 · NINDS · DUKE UNIVERSITY · PI SILVER, DEBRA · 2013 to 2023
$3.4MThe impact of human RNA diversity on protein production and cell fateDP2GM132932 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FLOOR, STEPHEN NICHOLAS · 2018 to 2018
$2.4MDistal mRNA localization and translation in neural stem cells of the developing brainR01NS110388 · NINDS · DUKE UNIVERSITY · PI SILVER, DEBRA · 2018 to 2022
$1.8MPost-transcriptional RNA regulation in mammalian neural stem cellsR21NS098176 · NINDS · DUKE UNIVERSITY · PI SILVER, DEBRA · 2017 to 2018
$437kThe Role of an Intellectual Disability Gene, DDX3X, In Neural Progenitors During Brain DevelopmentF32NS112566 · NINDS · DUKE UNIVERSITY · PI HOYE, MARIAH LAWLER · 2019 to 2022
$196kRNA localization in neural stem cells during cortical developmentF31NS093762 · NINDS · DUKE UNIVERSITY · PI LENNOX, ASHLEY · 2016 to 2017
$73kNIGMS NIH HHS DP2 GM132932NIGMS NIH HHS T32 GM007184NIGMS NIH HHS T32 GM007618NINDS NIH HHS F31 NS093762NINDS NIH HHS F32 NS112566NINDS NIH HHS R01 NS050375NINDS NIH HHS R01 NS058721NINDS NIH HHS R01 NS083897NINDS NIH HHS R01 NS110388NINDS NIH HHS R21 NS098176
Abstract
De novo germline mutations in the RNA helicase DDX3X account for 1%-3% of unexplained intellectual disability (ID) cases in females and are associated with autism, brain malformations, and epilepsy. Yet, the developmental and molecular mechanisms by which DDX3X mutations impair brain function are unknown. Here, we use human and mouse genetics and cell biological and biochemical approaches to elucidate mechanisms by which pathogenic DDX3X variants disrupt brain development. We report the largest clinical cohort to date with DDX3X mutations (n = 107), demonstrating a striking correlation between recurrent dominant missense mutations, polymicrogyria, and the most severe clinical outcomes. We show that Ddx3x controls cortical development by regulating neuron generation. Severe DDX3X missense mutations profoundly disrupt RNA helicase activity, induce ectopic RNA-protein granules in neural progenitors and neurons, and impair translation. Together, these results uncover key mechanisms underlying DDX3X syndrome and highlight aberrant RNA metabolism in the pathogenesis of neurodevelopmental disease.
Indexed as
Mutation, MissenseNeurogenesisAnimalsCell Line, TumorCells, CulturedCerebral CortexDEAD-box RNA HelicasesFemaleHumansMaleMiceMice, Inbred C57BLNeurodevelopmental DisordersRNADDX3X protein, humanDEAD-box RNA HelicasesRNAautismcorpus callosumcortical developmentDDX3Xhelicaseintellectual disabilitypolymicrogyriaradial glial progenitorstress granuletranslation
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