ArticleNeuron2019
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.
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Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 78 citations in OpenAlex.
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- TRIM71 mutations cause a neurodevelopmental syndrome featuring ventriculomegaly and hydrocephalus.Brain : a journal of neurology · 2024Article
- EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis.Circulation research · 2024Article
- [Use of ultrasound in vein of Galen malformation].Revista medica del Instituto Mexicano del Seguro Social · 2024Article
- Multidisciplinary care of fetal vein of Galen arteriovenous malformation diagnosed via Doppler ultrasound and magnetic resonance imaging: A case report.Case reports in women's health · 2024Article
- Update on the Vein of Galen Aneurysmal Malformation : Disease Concept and Genetics.Journal of Korean Neurosurgical Society · 2024Article
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- Pediatric Cerebral Vascular Malformations : Current and Future Perspectives.Journal of Korean Neurosurgical Society · 2024Article
- A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus.Brain : a journal of neurology · 2024Article
- Discovery and Characterization of Ephrin B2 and EphB4 Dysregulation and Novel Mutations in Cerebral Cavernous Malformations: In Vitro and Patient-Derived Evidence of Ephrin-Mediated Endothelial Cell Pathophysiology.Cellular and molecular neurobiology · 2023Article
- An EPHB4-RASA1 signaling complex inhibits shear stress-induced Ras-MAPK activation in lymphatic endothelial cells to promote the development of lymphatic vessel valves.bioRxiv : the preprint server for biology · 2023Article
- Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.Nature communications · 2023Article
- Temporospatial inhibition of Erk signaling is required for lymphatic valve formation.Signal transduction and targeted therapy · 2023Article
- Molecular genetics of human developmental neurocranial anomalies: towards "precision surgery".Cerebral cortex (New York, N.Y. : 1991) · 2023Article
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Authors and funding
47 authors at 17 institutions in 6 countries.
Daniel DuranDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Xue ZengDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Sheng Chih JinDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Jungmin ChoiDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Carol Nelson-WilliamsDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Bogdan YatsulaDepartment of Surgery, Yale School of Medicine, New Haven, CT, USA.
Jonathan GaillardDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Charuta Gavankar FureyDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Qiongshi LuDepartment of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
Andrew T TimberlakeDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Weilai DongDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Michelle A SorscherDepartment of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Erin LoringDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA.
Jennifer KleinDepartment of Neurosurgery, Boston Children's Hospital, Boston, MA, USA.
August AlloccoDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Ava HuntDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Sierra ConineDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Jason K KarimyDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Mark W YoungbloodDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA; Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
Jinwei ZhangInstitute of Biomedical and Clinical Sciences, University of Exeter Medical School, Hatherly Laboratory, Exeter, UK.
Michael L DiLunaDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Charles C MatoukDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA.
Shrikant ManeYale Center for Genome Analysis, West Haven, CT, USA.
Irina R TikhonovaYale Center for Genome Analysis, West Haven, CT, USA.
Christopher CastaldiYale Center for Genome Analysis, West Haven, CT, USA.
Francesc López-GiráldezYale Center for Genome Analysis, West Haven, CT, USA.
James KnightYale Center for Genome Analysis, West Haven, CT, USA.
Shozeb HaiderUniversity College London, School of Pharmacy, London, UK.
Mariya SobanUniversity College London, School of Pharmacy, London, UK; Department of Biochemistry, Aligarh Muslim University, Aligarh, India.
Seth L AlperDivision of Nephrology and Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston, MA, USA.
Masaki KomiyamaDepartment of Neurointervention, Osaka City General Hospital, Osaka, Japan.
Andrew F DucruetDepartment of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.
Joseph M ZabramskiDepartment of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.
Alan DardikDepartment of Surgery, Yale School of Medicine, New Haven, CT, USA.
Brian P WalcottDepartment of Neurological Surgery, University of Southern California, Los Angeles, CA, USA.
Christopher J StapletonDepartment of Neurological Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Beverly Aagaard-KienitzDepartment of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
Georges RodeschService de Neuroradiologie Diagnostique et Thérapeutique, Hôpital Foch, Suresnes, France.
Eric JacksonDepartment of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Edward R SmithDepartment of Neurointerventional Radiology, Boston Children's Hospital, Boston, MA, USA.
Darren B OrbachDepartment of Neurosurgery, Boston Children's Hospital, Boston, MA, USA; Department of Neurointerventional Radiology, Boston Children's Hospital, Boston, MA, USA.
Alejandro BerensteinDepartment of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Kaya BilguvarDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA; Yale Center for Genome Analysis, West Haven, CT, USA.
Miikka VikkulaHuman Molecular Genetics, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.
Murat GunelDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA; Department of Genetics, Yale School of Medicine, New Haven, CT, USA.
Richard P LiftonDepartment of Genetics, Yale School of Medicine, New Haven, CT, USA; Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, USA.
Kristopher T KahleDepartment of Neurosurgery, Yale School of Medicine, New Haven, CT, USA; Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA. Electronic address: kristopher.kahle@yale.edu.
Yale University · USYale Cancer Center · USBoston Children's Hospital · USBarrow Neurological Institute · USIcahn School of Medicine at Mount Sinai · USRockefeller University · USUniversity of Wisconsin–Madison · USAligarh Muslim University · INBeth Israel Deaconess Medical Center · USde Duve Institute · BEHôpital Foch · FRJohns Hopkins University · USNeurological Surgery · USOsaka City General Hospital · JPUniversity College London · GBUniversity of Exeter · GBUniversity of Southern California · US
Funding
Yale Center for Mendelian DisordersU54HG006504 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER, GUNEL, MURAT · 2012 to 2015
$11.0MHuman Genetics and Molecular Mechanisms of Vein of Galen Aneurysmal MalformationR01NS117609 · NINDS · YALE UNIVERSITY · PI Titus Jonathon Boggon, Kristopher T. Kahle · 2020 to 2026
$3.3MHigh Performance Computing Instrumentation for the Yale Center for Genome AnalysiS10OD018521 · OD · YALE UNIVERSITY · PI MANE, SHRIKANT M · 2015 to 2015
$890kNHGRI NIH HHS U54 HG006504NIH HHS S10 OD018521NINDS NIH HHS R01 NS117609
Abstract
Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.
Indexed as
MutationChromatin Assembly and DisassemblyEphrinsFemaleHumansMaleMembrane GlycoproteinsMetalloendopeptidasesPedigreePenetranceReceptor, EphB4Signal TransductionVein of Galen MalformationsEphrinsKEL protein, humanMembrane GlycoproteinsMetalloendopeptidasesReceptor, EphB4arterio-venous malformationchromatin modifierde novo mutationsEPHB4ephrin signalingpediatric neurosurgeryVein of Galen malformationwhole exome sequencing
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