ArticleNature medicine2020
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus.
Open access · bronzeAbstract read
In one paragraph
Article in Nature medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 3 pooled it
28.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Multi-omics and high-spatial-resolution omics: deciphering complexity in neurological disorders.GigaScience · 2025Pooled it
- Molecular Diagnostic Yield of Exome Sequencing in Patients With Congenital Hydrocephalus: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Pathophysiologic mechanisms and strategies for the treatment of post-hemorrhagic hydrocephalus of prematurity.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2022Pooled it
- Chiari I malformation.Nature reviews. Disease primers · 2026Review
- De novo variants in LDB1 are linked to distinct neurodevelopmental phenotypes determined by variant location and differing pathomechanisms.American journal of human genetics · 2026Article
- Prenatal diagnosis of Apert syndrome caused by a de novo FGFR2 mutation in the second trimester: a case report.BMC pregnancy and childbirth · 2026Article
- Sequential sequencing reveals the architecture and complexity of genomic variants in patients with Alport syndrome.Nature communications · 2026Article
- Genome admixture analysis of 1,030 Ugandan infants with neonatal sepsis and hydrocephalus demonstrates geographical stratification of population disease risk.medRxiv : the preprint server for health sciences · 2026Article
- Identification and validation of CARS1 p.E712V and NF1 p.Q2002X in sporadic Moyamoya disease across 30 trio pedigrees.NPJ genomic medicine · 2026Article
- Biallelic TruncatingInternational journal of molecular sciences · 2026Review
- De NovoHuman mutation · 2026Article
- Shunt Complications in Syndromic versus Non-Syndromic Pediatric Hydrocephalus: A Propensity-Matched Multicenter Analysis of 35,234 Patients.Pediatric neurosurgery · 2026Article
- Novel histone deacetylase 6 gene variant is associated with fetal hydrocephalus and lateral ventriculomegaly.American journal of translational research · 2026Article
- Fetal mri of obstructive hydrocephalus: a review proposing a surgical etiology-based approach.Neuroradiology · 2026Review
- Functional Profiling ofCirculation. Genomic and precision medicine · 2025Article
- Recessive genomic and phenotypic variation in consanguineous families with cerebral palsy.medRxiv : the preprint server for health sciences · 2025Article
- Preclinical evaluation of antisense oligonucleotide therapy in a mouse model ofbioRxiv : the preprint server for biology · 2025Article
- SomaticGenes · 2025Article
- Review
- The RNA-binding protein TRIM71 is essential for hearing in humans and mice and times auditory sensory organ development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
61 authors at 20 institutions in 5 countries.
Sheng Chih Jin *Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-5777-7262
Weilai Dong *Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.ORCID http://orcid.org/0000-0002-8376-1758
Adam J Kundishora *Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Shreyas Panchagnula *Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Andres Moreno-De-Luca *Autism & Developmental Medicine Institute, Genomic Medicine Institute, Department of Radiology, Geisinger, Danville, PA, USA.ORCID http://orcid.org/0000-0002-2732-4043
Charuta G FureyDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
August A AlloccoDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Rebecca L WalkerDepartment of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Carol Nelson-WilliamsDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0768-4751
Hannah SmithDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Ashley DunbarDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Sierra ConineDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Qiongshi LuDepartment of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0002-4514-0969
Xue ZengLaboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Michael C SierantLaboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
James R KnightDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-1166-0437
William SullivanDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Phan Q DuyDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-4513-7348
Tyrone DeSpenzaDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Benjamin C ReevesDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5924-6991
Jason K KarimyDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Arnaud MarlierDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Christopher CastaldiYale Center for Genome Analysis, Yale University, New Haven, CT, USA.
Irina R TikhonovaYale Center for Genome Analysis, Yale University, New Haven, CT, USA.
Boyang LiDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Helena Perez PeñaDepartment of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, UK.ORCID http://orcid.org/0000-0001-7938-4307
James R BroachInstitute for Personalized Medicine, The Penn State College of Medicine, Hershey, PA, USA.ORCID http://orcid.org/0000-0003-1197-0312
Edith M KabachelorCURE Children's Hospital of Uganda, Mbale, Uganda.
Peter SsenyongaCURE Children's Hospital of Uganda, Mbale, Uganda.
Christine HehnlyDepartments of Neurosurgery, Engineering Science & Mechanics, and Physics; Center for Neural Engineering and Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA, USA.ORCID http://orcid.org/0000-0003-3739-0690
Li GeDepartment of Biostatistics & Medical Informatics, University of Wisconsin, Madison, WI, USA.ORCID http://orcid.org/0000-0001-7651-134X
Boris KerenDépartement de Génétique, Centre de Référence Déficiences Intellectuelles de Causes Rares, Groupe Hospitalier Pitié Salpêtrière et GHUEP Hôpital Trousseau, Sorbonne Université, GRC "Déficience Intellectuelle et Autisme", Paris, France.
Andrew T TimberlakeHansjörg Wyss Department of Plastic Surgery, New York University Langone Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-8926-9692
June GotoDivision of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-4000-9750
Francesco T ManganoDivision of Pediatric Neurosurgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
James M JohnstonDepartment of Neurosurgery, University of Alabama School of Medicine, Birmingham, AL, USA.
William E ButlerDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Benjamin C WarfDepartment of Neurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Edward R SmithDepartment of Neurosurgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Steven J SchiffDepartments of Neurosurgery, Engineering Science & Mechanics, and Physics; Center for Neural Engineering and Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA, USA.
David D LimbrickDepartment of Neurological Surgery and Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.
Gregory HeuerDepartment of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Eric M JacksonDepartment of Neurosurgery, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9306-9290
Bermans J IskandarDepartment of Neurological Surgery, University of Wisconsin Medical School, Madison, WI, USA.
Shrikant ManeDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Shozeb HaiderDepartment of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, UK.ORCID http://orcid.org/0000-0003-2650-2925
Bulent GucluKartal Dr. Lutfi Kirdar Research and Training Hospital, Istanbul, Turkey.
Yasar BayriDepartment of Neurosurgery, Marmara University School of Medicine, Istanbul, Turkey.
Yener SahinDepartment of Neurosurgery, Marmara University School of Medicine, Istanbul, Turkey.
Charles C DuncanDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Michael L J ApuzzoDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Michael L DiLunaDepartment of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA.
Ellen J HoffmanYale Child Study Center, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-5083-1369
Nenad SestanDepartment of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0966-9619
Laura R MentDepartment of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Seth L AlperDivision of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6228-2512
Kaya BilguvarDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.
Daniel H GeschwindDepartment of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2896-3450
Murat GünelDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2290-7055
Richard P LiftonLaboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Kristopher T KahleDepartment of Genetics, Yale University School of Medicine, New Haven, CT, USA. kristopher.kahle@yale.edu.ORCID http://orcid.org/0000-0002-5922-7547
Yale University · USPennsylvania State University · USBoston Children's Hospital · USCincinnati Children's Hospital Medical Center · USCURE Children’s Hospital of Uganda · UGMarmara University · TRNeurological Surgery · USUniversity College London · GBUniversity of California, Los Angeles · USUniversity of Wisconsin–Madison · USAutism & Developmental Medicine Institute · USBarrow Neurological Institute · USBeth Israel Deaconess Medical Center · USChildren's Hospital of Philadelphia · USDr Lütfi Kırdar Kartal Eğitim ve Araştırma Hastanesi · TRHarvard University · USJohns Hopkins University · USNYU Langone Health · USSorbonne Université · FRUniversity of Alabama · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MMEDICAL SCIENTIST TRAINING PROGRAMT32GM007205 · NIGMS · YALE UNIVERSITY · PI KAZMIERCZAK, BARBARA I · 1985 to 2019
$42.9MYale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0MNRSA Training CoreTL1TR001864 · NCATS · YALE UNIVERSITY · PI CANTLEY, LLOYD G, EDELMAN, E. JENNIFER · 2016 to 2025
$9.9MGENETICS AND GENOMICS OF HUMAN DISEASET32HD007149 · NICHD · YALE UNIVERSITY · PI James P Noonan · 1985 to 2026
$8.2MPredictive Personalized Public Health (P3H): A Novel Paradigm to Treat Infectious DiseaseR01AI145057 · NIAID · YALE UNIVERSITY · PI SCHIFF, STEVEN J · 2018 to 2022
$8.1MControl of the Neonatal Septisome and Hydrocephalus in sub-Saharan AfricaDP1HD086071 · NICHD · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SCHIFF, STEVEN J · 2015 to 2019
$4.1MHuman Genetics and Molecular Mechanisms of Congenital HydrocephalusR01NS111029 · NINDS · YALE UNIVERSITY · PI DENIZ, ENGIN, JIN, SHENG CHIH · 2020 to 2024
$2.5MModulation of Choroid Plexus Immuno-secretory Function to Restore Cerebrospinal Fluid Homeostasis in HydrocephalusR01NS109358 · NINDS · YALE UNIVERSITY · PI Kristopher T. Kahle · 2018 to 2026
$2.4MIntegrative Genomic Analysis of Congenital Heart DiseaseR00HL143036 · NHLBI · WASHINGTON UNIVERSITY · PI JIN, SHENG CHIH · 2020 to 2022
$730kIntegrative Genomic Analysis of Congenital Heart DiseaseK99HL143036 · NHLBI · ROCKEFELLER UNIVERSITY · PI JIN, SHENG CHIH · 2019 to 2019
$178kThe Role of Pten in Congenital HydrocephalusF31NS115519 · NINDS · YALE UNIVERSITY · PI DESPENZA, TYRONE · 2020 to 2022
$62kNCATS NIH HHS TL1 TR001864NCATS NIH HHS UL1 TR001863NHGRI NIH HHS U54 HG006504NHLBI NIH HHS K99 HL143036NHLBI NIH HHS R00 HL143036NIAID NIH HHS R01 AI145057NICHD NIH HHS DP1 HD086071NICHD NIH HHS T32 HD007149NIGMS NIH HHS T32 GM007205NINDS NIH HHS F31 NS115519NINDS NIH HHS R01 NS109358NINDS NIH HHS R01 NS111029
Abstract
Congenital hydrocephalus (CH), characterized by enlarged brain ventricles, is considered a disease of excessive cerebrospinal fluid (CSF) accumulation and thereby treated with neurosurgical CSF diversion with high morbidity and failure rates. The poor neurodevelopmental outcomes and persistence of ventriculomegaly in some post-surgical patients highlight our limited knowledge of disease mechanisms. Through whole-exome sequencing of 381 patients (232 trios) with sporadic, neurosurgically treated CH, we found that damaging de novo mutations account for >17% of cases, with five different genes exhibiting a significant de novo mutation burden. In all, rare, damaging mutations with large effect contributed to ~22% of sporadic CH cases. Multiple CH genes are key regulators of neural stem cell biology and converge in human transcriptional networks and cell types pertinent for fetal neuro-gliogenesis. These data implicate genetic disruption of early brain development, not impaired CSF dynamics, as the primary pathomechanism of a significant number of patients with sporadic CH.
Indexed as
Genetic Predisposition to DiseaseBrainCerebral VentriclesExomeExome SequencingFemaleHumansHydrocephalusMaleMutationNeural Stem CellsNeurogenesisNeurogliaTranscription FactorsTripartite Motif ProteinsUbiquitin-Protein LigasesSMARCC1 protein, humanTranscription FactorsTRIM71 protein, humanTripartite Motif ProteinsUbiquitin-Protein Ligases
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.