ArticleAmerican journal of human genetics2023
Bi-allelic variants in the ESAM tight-junction gene cause a neurodevelopmental disorder associated with fetal intracranial hemorrhage.
Open access · greenAbstract read
In one paragraph
Article in American journal of human genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.9field-weighted citation impact, top 9% 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
14 citing papers in PubMed, 14 citations in OpenAlex.
- Cellular and signalling mechanisms that regulate the blood-brain barrier.Nature reviews. Molecular cell biology · 2026Review
- Genetics of intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Phenotypic Refinement of ESAM-Related Tight-Junctionopathy: Novel Genetic and Ocular Findings and Literature Review.Molecular genetics & genomic medicine · 2026Review
- Spatial distribution of blood-brain barrier membrane proteins is controlled by sorting motifs and physiological signals in vivo.bioRxiv : the preprint server for biology · 2026Article
- Article
- Fetal intracerebral hemorrhage: review of the literature and practice considerations.Pediatric research · 2025Review
- The Triad of Blood-Brain Barrier Integrity: Endothelial Cells, Astrocytes, and Pericytes in Perinatal Stroke Pathophysiology.International journal of molecular sciences · 2025Review
- Novel homozygous ESAM variants in two families with perinatal strokes showing variable neuroradiologic and clinical findings.Journal of human genetics · 2025Article
- GREGoR: Accelerating Genomics for Rare Diseases.ArXiv · 2024Article
- Further evidence supporting the role of GTDC1 in glycine metabolism and neurodevelopmental disorders.European journal of human genetics : EJHG · 2024Article
- Gain-of-function mutations of TRPV4 acting in endothelial cells drive blood-CNS barrier breakdown and motor neuron degeneration in mice.Science translational medicine · 2024Article
- Genomic analysis of presumed perinatal stroke in Saudi Arabia reveals a strong monogenic contribution.Human genetics · 2024Article
- Neurodevelopmental disorders: 2024 update.Free neuropathology · 2024Article
- Extraretinal Fibrovascular Proliferation in a Neonate Possibly Associated with anTurkish journal of ophthalmology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
47 authors at 20 institutions in 11 countries.
Mauro LeccaDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Davut PehlivanSection of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA.
Damià Heine SuñerMolecular Diagnostics and Clinical Genetics Unit, Hospital Universitari Son Espases, Palma, Illes Balears, Spain; Genomics of Health, Institute of Health Research of the Balearic Islands, Palma, Illes Balears, Spain.
Karin WeissGenetics Institute, Rambam Health Care Campus, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Thibault CosteAP-HP, Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis, Paris, France; Université de Paris, INSERM UMR-1141 Neurodiderot, Paris, France.
Markus ZweierInstitute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland.
Yavuz OktayIzmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir 35340, Turkey; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey; Department of Medical Biology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey.
Nada Danial-FarranThe Genetic Institute, Emek Medical Center, Afula, Israel.
Vittorio RostiCenter for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Maria Paola BonasoniPathology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Alessandro MalaraDepartment of Molecular Medicine, University of Pavia, Pavia, Italy; Laboratory of Biochemistry-Biotechnology and Advanced Diagnostics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
Gianluca ContròMedical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Roberta ZuntiniMedical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Marzia PollazzonMedical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Rosario PascarellaNeuroradiology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Alberto NeriOphthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Carlo FuscoChild Neurology and Psychiatry Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Dana MarafiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Tadahiro MitaniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Jennifer Ellen PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Sadik Etka BayramogluTertiary ROP Center, Health Science University Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey.
Alper GezdiriciDepartment of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul 34480, Turkey.
Jessica Hernandez-RodriguezGenomics of Health, Institute of Health Research of the Balearic Islands, Palma, Illes Balears, Spain.
Emilia Amengual CladeraGenomics of Health, Institute of Health Research of the Balearic Islands, Palma, Illes Balears, Spain.
Elena MiravetMetabolic Pathologies and Pediatric Neurology Unit, Pediatric Service, Hospital Universitari Son Espases, Palma, Illes Balears, Spain.
Jorge Roldan-BustoPediatric Radiology Unit, Radiology Service, Hospital Universitari Son Espases, Palma, Illes Balears, Spain.
María Angeles RuizMetabolic Pathologies and Pediatric Neurology Unit, Pediatric Service, Hospital Universitari Son Espases, Palma, Illes Balears, Spain.
Cristofol Vives BauzáNeurobiology, Institute of Health Research of the Balearic Islands, Palma, Illes Balears, Spain.
Liat Ben-SiraDepartment of Radiology, Division of Pediatric Radiology, Dana Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel.
Sabine SigaudyAP-HM, Service de Génétique, Hôpital de la Timone, Marseille, France.
Anaïs BegemannInstitute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland.
Sheila UngerMedical Genetics Service, CHUV, University of Lausanne, Lausanne, Switzerland.
Serdal GüngörInonu University, Faculty of Medicine, Turgut Ozal Research Center, Department of Pediatric Neurology, Malatya, Turkey.
Semra HizIzmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey; Department of Pediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey.
Ece SonmezlerIzmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir 35340, Turkey; Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey.
Yoav ZehaviThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Department of Pediatrics B, Emek Medical Center, Afula, Israel.
Michael JerdevPoriya Medical Center and the Azrieli Faculty of Medicine, Bar-Ilan University, Ramat-Gan, Israel.
Alessandra BalduiniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
Orsetta ZuffardiDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Rita HorvathDepartment of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK; Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0PY, UK.
Hanns LochmüllerChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa ON K1H 8L1, Canada; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, ON K1H 8L1, Canada.
Anita RauchInstitute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland; University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland.
Livia GaravelliMedical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Elisabeth Tournier-LasserveAP-HP, Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis, Paris, France; Université de Paris, INSERM UMR-1141 Neurodiderot, Paris, France.
Ronen SpiegelThe Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; Department of Pediatrics B, Emek Medical Center, Afula, Israel.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
Edoardo ErrichielloDepartment of Molecular Medicine, University of Pavia, Pavia, Italy; Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy. Electronic address: edoardo.errichiello@unipv.it.
Azienda Sanitaria Unità Locale di Reggio Emilia · ITBaylor College of Medicine · USHealth Research Institute of the Balearic Islands · ESUniversity of Pavia · ITHospital Universitario Son Espases · ESTechnion – Israel Institute of Technology · ILUniversity of Zurich · CHDokuz Eylül University · TRInserm · FRBar-Ilan University · ILEmek Medical Center · ILHôpital de la Timone · FRInonu University · TRIstanbul Metropolitan Municipality · TRIzmir University · TRPoliclinico San Matteo Fondazione · ITSağlık Bilimleri Üniversitesi · TRTel Aviv University · ILTufts University · USUniversity of Cambridge · GB
Funding
Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MFrequency of variants of unknown significance by ancestry groups in the All of Us Research Program cohortU01HG011758 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI RICHARD A GIBBS, JAMES R. LUPSKI · 2021 to 2026
$13.8MMEDICAL GENETICS RESEARCH FELLOWSHIP PROGRAMT32GM007526 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI Brendan Lee · 1985 to 2026
$11.4MSTRUCTURAL VARIATION IN NEUROLOGICAL DISEASER35NS105078 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2018 to 2025
$6.0MComprehensive Deep Phenotyping and Multi-omics to Develop Clinical and Molecular Biomarkers for MeCP2-related DiseasesK23NS125126 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI Davut Pehlivan · 2022 to 2026
$1.1MIndividual genomic analyses to discover the molecular basis and mechanisms contributing to adult-onset diseaseK08HG008986 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI POSEY, JENNIFER ELLEN · 2017 to 2021
$831kNHGRI NIH HHS K08 HG008986NHGRI NIH HHS U01 HG011758NINDS NIH HHS K23 NS125126NINDS NIH HHS R35 NS105078
Abstract
The blood-brain barrier (BBB) is an essential gatekeeper for the central nervous system and incidence of neurodevelopmental disorders (NDDs) is higher in infants with a history of intracerebral hemorrhage (ICH). We discovered a rare disease trait in thirteen individuals, including four fetuses, from eight unrelated families associated with homozygous loss-of-function variant alleles of ESAM which encodes an endothelial cell adhesion molecule. The c.115del (p.Arg39Glyfs
Indexed as
Brain DiseasesCell Adhesion MoleculesNervous System MalformationsNeurodevelopmental DisordersAllelesAnimalsEndothelial CellsHumansIntracranial HemorrhagesMiceTight JunctionsCell Adhesion MoleculesESAM protein, humanEsam protein, mouseblood-brain barrierepilepsyESAMexome sequencingglobal developmental delayintellectual disabilityintracranial hemorrhageneurodevelopmental disorderspregnancy lossretinopathytight junctions
Identifiers
What Socratic holds
Textmetadata
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 Socratic graph.