ArticleNature genetics2023
Comprehensive multi-omic profiling of somatic mutations in malformations of cortical development.
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Article in Nature genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78citing papers in PubMed
15.7field-weighted citation impact, top 1% of its field
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Who cites it
78 citing papers in PubMed, 103 citations in OpenAlex.
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- Targeted interneuron ablation in an mTORopathy model: Testing a two-hit mechanism of epileptogenesis.Progress in neurobiology · 2026Article
- Drug resistant epilepsy driven byEpilepsy & behavior reports · 2026Article
- Decoding epilepsy's molecular blueprint: Machine learning unravels transcriptomic subtypes and regulatory networks.Epilepsia · 2026Article
- Radiogenomics of congenital brain malformations: Linking embryology, genetics, and imaging.Neuroradiology · 2026Review
- Somatic mosaicism in ALS and FTD identifies focal mutations associated with widespread degeneration.Nature genetics · 2026Article
- Excitatory neurons and astrocytes-specific dysregulation and aberrant interactions are vulnerable to FCDI as suggested by single-cell spatial transcriptomics.Clinical and translational medicine · 2026Article
- Disease insights from brain somatic mosaicism.Experimental & molecular medicine · 2026Review
- Spatial transcriptomics in epilepsy research: Early successes, opportunities, and challenges.Epilepsia · 2026Article
- AI in epilepsy neuroimaging.Current opinion in neurology · 2026Review
- Dysmorphic neurons express markers of inhibitory glycinergic signaling in focal cortical dysplasia IIb.Brain pathology (Zurich, Switzerland) · 2026Article
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- Areas of research priorities in epilepsy: A position paper of the European Reference Network for Rare and Complex Epilepsies, EpiCARE.Epilepsia open · 2026Article
- Integrated Multi-Omics Profiling Identifies CD84-Associated Microglial Alterations in Focal Cortical Dysplasia Type II.Journal of inflammation research · 2026Article
- Prenatal MRI features of fetal complete agenesis of the corpus callosum associated with unilateral hemispheric cortical malformation: a retrospective study.Frontiers in radiology · 2026Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
53 authors at 20 institutions in 12 countries.
Changuk Chung *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Xiaoxu Yang *Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0219-0023
Taejeong BaeDepartment of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Keng Ioi VongDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5377-9845
Swapnil MittalDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Catharina DonkelsDepartment of Neurosurgery, Experimental Epilepsy Research, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0003-2636-3873
H Westley PhillipsDepartment of Neurosurgery, University of California at Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-0512-4590
Zhen LiDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Ashley P L MarshDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Martin W BreussDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Laurel L BallDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Camila Araújo Bernardino GarciaLaboratory of Pediatric Neurosurgery and Developmental Neuropathology, Department of Surgery and Anatomy, University of São Paulo, Ribeirão Preto, Brazil.
Renee D GeorgeDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Jing GuDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Mingchu XuDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Chelsea BarrowsDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Kiely N JamesDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Valentina StanleyDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Anna S NidhiryDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Sami KhouryDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Gabrielle HoweDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Emily RileyDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Xin XuDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Brett CopelandDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Yifan WangDepartment of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.
Se Hoon KimDepartment of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.ORCID http://orcid.org/0000-0001-7516-7372
Hoon-Chul KangDivision of Pediatric Neurology, Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, South Korea.
Andreas Schulze-BonhageCenter for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Carola A HaasDepartment of Neurosurgery, Experimental Epilepsy Research, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Horst UrbachDepartment of Neuroradiology, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.
Marco PrinzCenter for Basics in NeuroModulation, Faculty of Medicine, University of Freiburg, Freiburg, Germany.ORCID http://orcid.org/0000-0002-0349-1955
David D LimbrickDepartment of Neurology, St. Louis Children's Hospital, Washington University St Louis, Washington, MO, USA.
Christina A GurnettDepartment of Neurology, St. Louis Children's Hospital, Washington University St Louis, Washington, MO, USA.
Matthew D SmythDepartment of Neurosurgery, St. Louis Children's Hospital, Washington University St Louis, Washington, MO, USA.
Shifteh SattarEpilepsy Center, Rady Children's Hospital, San Diego, CA, USA.
Mark NespecaEpilepsy Center, Rady Children's Hospital, San Diego, CA, USA.
David D GondaEpilepsy Center, Rady Children's Hospital, San Diego, CA, USA.
Katsumi ImaiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Yukitoshi TakahashiNational Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Hsin-Hung ChenDivision of Pediatric Neurosurgery, The Neurological Institute, Taipei Veterans General Hospital, Taipei City, Taiwan.ORCID http://orcid.org/0000-0001-7531-9188
Jin-Wu TsaiInstitute of Brain Science, Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Valerio ContiPediatric Neurology Unit and Laboratories, IRCCS Meyer Children's Hospital University of Florence, Firenze, Italy.
Renzo GuerriniPediatric Neurology Unit and Laboratories, IRCCS Meyer Children's Hospital University of Florence, Firenze, Italy.
Orrin DevinskyComprehensive Epilepsy Center, Department of Neurology, New York University Langone Health, New York, NY, USA.
Wilson A SilvaDepartment of Genetics, Center for Cell-Based Therapy, Center for Integrative Systems Biology, University of São Paulo, Ribeirão Preto, Brazil.ORCID http://orcid.org/0000-0001-9364-2886
Helio R MachadoLaboratory of Pediatric Neurosurgery and Developmental Neuropathology, Department of Surgery and Anatomy, University of São Paulo, Ribeirão Preto, Brazil.
Gary W MathernDepartment of Neurosurgery, University of California at Los Angeles, Los Angeles, CA, USA.
Alexej AbyzovDepartment of Quantitative Health Sciences, Center for Individualized Medicine, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0001-5405-6729
Sara BaldassariSorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Paris, France.
Stéphanie BaulacSorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Hôpital de la Pitié Salpêtrière, Paris, France.
Focal Cortical Dysplasia Neurogenetics Consortium
Brain Somatic Mosaicism Network
Joseph G GleesonDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA. jogleeson@health.ucsd.edu.ORCID http://orcid.org/0000-0002-6713-8018
Children’s Institute · USBoston Children's Hospital · USHarvard University · USUniversity of Michigan · USRady Children's Hospital-San Diego · USUniversitat Pompeu Fabra · ESUniversity of Freiburg · DEYale University · USLieber Institute for Brain Development · USMayo Clinic · USUniversidade de São Paulo · BRSalk Institute for Biological Studies · USSt. Louis Children's Hospital · USUniversity of California, Los Angeles · USKennedy Krieger Institute · USMeyer Children's Hospital · ITNational Epilepsy Center · JPUniversity of California San Diego · USYonsei University · KRBarrow Neurological Institute · US
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MVIRAL MALIGNANCYP30CA023100 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DIANE M SIMEONE · 1985 to 2026
$124.9MJoint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MWUIDDRC Supplement-Supporting the health and well-being of children with intellectual and developmental disability during COVID-19 pandemicP50HD103525 · NICHD · WASHINGTON UNIVERSITY · PI JEFFREY D MILBRANDT · 2020 to 2026
$15.5MPREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3MYale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0MU of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0MMosaicism in focal cortical dysplasias spectrum seen in neuropsychiatric diseaseU01MH108898 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2015 to 2019
$5.1MMolecular characterization of HemimegalencephalyR01NS083823 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, MATHERN, GARY W. · 2013 to 2017
$3.1MClinGen Expert Curation Panel for the EpilepsiesU24NS120854 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Ingo Helbig, HEATHER C. MEFFORD · 2021 to 2026
$2.0MOrigins of Brain Somatic Mosaicism in Developmental Brain DiseaseR01MH124890 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G · 2021 to 2025
$1.5MIllumina NovaSeq 6000 Sequencing SystemS10OD026929 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JEPSEN, KRISTEN LYNN · 2019 to 2019
$600kNCI NIH HHS P30 CA023100NHGRI NIH HHS U54 HG003067NHGRI NIH HHS U54 HG006504NHGRI NIH HHS UM1 HG008900NIA NIH HHS R21 AG070462NICHD NIH HHS P50 HD103525NIGMS NIH HHS T32 GM007544NIH HHS S10 OD026929NIMH NIH HHS R01 MH124890NIMH NIH HHS U01 MH108898NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS083823NINDS NIH HHS U24 NS120854
Abstract
Malformations of cortical development (MCD) are neurological conditions involving focal disruptions of cortical architecture and cellular organization that arise during embryogenesis, largely from somatic mosaic mutations, and cause intractable epilepsy. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat condition-related epilepsy. Here we report a genetic landscape from 283 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation including in utero electroporation of mice and single-nucleus RNA sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associated with distinct pathophysiological and clinical phenotypes. The unique single-cell level spatiotemporal expression patterns of mutated genes in control and patient brains indicate critical roles in excitatory neurogenic pools during brain development and in promoting neuronal hyperexcitability after birth.
Indexed as
EpilepsyMalformations of Cortical DevelopmentBrainHumansMultiomicsMutation
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