ArticleJournal of Crohn's & colitis2021
Variants in STXBP3 are Associated with Very Early Onset Inflammatory Bowel Disease, Bilateral Sensorineural Hearing Loss and Immune Dysregulation.
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Article in Journal of Crohn's & colitis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12citing papers in PubMed
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- A case of cryopyrin-associated periodic syndrome presenting with abdominal symptoms due to a novel mutation NLRP3 p.Ile257Met.Clinical journal of gastroenterology · 2026Article
- An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans.Nature communications · 2026Article
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- UNCP-18 is amicroPublication biology · 2026Article
- The role of exome data reanalysis in clarifyingGastroenterology report · 2025Article
- Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.Inflammatory bowel diseases · 2024Review
- Current genetic diagnostics in inborn errors of immunity.Frontiers in pediatrics · 2024Review
- Sex differences in brain protein expression and disease.Nature medicine · 2023Article
- The regulatory role of alternative splicing in inflammatory bowel disease.Frontiers in immunology · 2023Review
- Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2022Article
- Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease.Frontiers in immunology · 2022Review
- STXBP3 and GOT2 predict immunological activity in acute allograft rejection.Frontiers in immunology · 2022Article
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Authors and funding
50 authors at 17 institutions in 7 countries.
Jodie OuahedDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Judith R KelsenDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Waldo A SpessottDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Kameron KoosheshBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Maria L SanmillanDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Noor DawanyDepartment of Biomedical Health Informatics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.
Kathleen E SullivanDivision of Allergy and Immunology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Kathryn E HamiltonDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Voytek SlowikDepartment of Medicine, Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sergey NejentsevDivision of Gastroenterology, Hepatology, and Nutrition, Children's Mercy Kansas City, Kansas City, MO, 64108, USA.
João Farela NevesDepartment of Molecular Cell Biology and Immunology, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
Helena FloresCEDOC, Chronic Diseases Research Center, NOVA Medical School, Lisbon, 1150, Portugal.
Wendy K ChungGastroenterology Unit, Hospital Dona Estefânia-CHLC, EPE, Lisbon, 1169, Portugal.
Ashley WilsonGastroenterology Unit, Hospital Dona Estefânia-CHLC, EPE, Lisbon, 1169, Portugal.
Kwame Anyane-YeboaGastroenterology Unit, Hospital Dona Estefânia-CHLC, EPE, Lisbon, 1169, Portugal.
Karen WouGastroenterology Unit, Hospital Dona Estefânia-CHLC, EPE, Lisbon, 1169, Portugal.
Preti JainDepartment of Pediatrics, Columbia University Medical Center, New York, NY, 10032, USA.
Michael FieldDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Sophia TollefsonDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Maiah H DentDepartment of Genetics, Yale University, New Haven, CT, 06510, USA.
Dalin LiF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Takeo NaitoF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Andrew C KwongDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Faith TaliaferroDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Jose Ordovas-MontanesDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Bruce H HorwitzDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Daniel KotlarzDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Christoph KleinDr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital LMU Munich, Munich, 80337, Germany.
Jonathan EvansDepartment of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL 32207, USA.
Jill DorseyDepartment of Pediatrics, Nemours Children's Specialty Care, Jacksonville, FL 32207, USA.
Neil WarnerSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
Abdul ElkadriSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
Aleixo M MuiseSickKids Inflammatory Bowel Disease Center and Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.ORCID 0000-0001-9624-3346
Jeffrey GoldsmithDepartment of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Benjamin ThompsonPrimary Immunodeficiency Group, III Theme, Institute of Cellular Medicine, Newcastle University, Newcastle, NE2 4HH, UK.
Karin R EngelhardtPrimary Immunodeficiency Group, III Theme, Institute of Cellular Medicine, Newcastle University, Newcastle, NE2 4HH, UK.
Andrew J CantPrimary Immunodeficiency Group, III Theme, Institute of Cellular Medicine, Newcastle University, Newcastle, NE2 4HH, UK.
Sophie HambletonPrimary Immunodeficiency Group, III Theme, Institute of Cellular Medicine, Newcastle University, Newcastle, NE2 4HH, UK.
Andrew BarclayDepartment of Paediatric Gastroenterology, Royal Hospital for Children, Glasgow, G51 4TF, UK.
Agnes Toth-PetroczyBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Dana VuzmanBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Nikkola CarmichaelBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Corneliu BodeaBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Christopher A CassaBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Marcella DevotoDivision of Human Genetics, The Children's Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Richard L MaasBrigham Genomic Medicine Program, Division of Genetics, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Edward M BehrensDivision of Rheumatology, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Claudio G GiraudoDepartment of Microbiology and Immunology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Scott B SnapperDivision of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Boston Children's Hospital, and Harvard Medical School, Boston, MA, 02115, USA.
Brigham and Women's Hospital · USBoston Children's Hospital · USChildren's Hospital of Philadelphia · USHospital de Dona Estefânia · PTBroad Institute · USCedars-Sinai Medical Center · USThomas Jefferson University · USUniversity of Toronto · CANewcastle University · GBNewcastle upon Tyne Hospitals NHS Foundation Trust · GBChildren's Mercy Hospital · USColumbia University Irving Medical Center · USLMU Klinikum · DERoyal Hospital for Children · GBUniversidade Nova de Lisboa · PTUniversity of Pennsylvania · USYale University · US
Funding
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MSTRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4MCOngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8MIntegrated pathogenicity assessment of clinically actionable genetic variantsR01HG010372 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI CASSA, CHRISTOPHER · 2018 to 2022
$3.5MRole of Interferon lambda signaling in mucosal homeostasis and infantile-onset inflammatory bowel diseaseK08DK122133 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI OUAHED, JODIE · 2020 to 2024
$896kVery Early-onset inflammatory bowel diseaseK23DK100461 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI KELSEN, JUDITH RACHEL · 2014 to 2018
$893kAn integrative approach to understanding the genetic basis of very early onset inflammatory bowel diseaseR01DK111843 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI KELSEN, JUDITH RACHEL · 2018 to 2020
$772kThe role of IMP1 mRNA binding protein in intestinal epithelial biologyK01DK100485 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI HAMILTON, KATHRYN ELIZABETH · 2014 to 2018
$631kIMP1 REGULATION OF AUTOPHAGY IN THE INTESTINAL EPITHELIUMR03DK114463 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI HAMILTON, KATHRYN ELIZABETH · 2017 to 2018
$156kBoston Children's HospitalDamon Runyon Cancer Research Foundation DRG-2274-16Helmsley Charitable TrustInstitute for Translational Medicine and TherapeuticsJPB FoundationNCATS NIH HHS UL1 TR001863NHGRI NIH HHS R01 HG010372NIDDK NIH HHS K01 DK100485NIDDK NIH HHS K08 DK122133NIDDK NIH HHS K23 DK100461NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R01 DK111843NIDDK NIH HHS R03 DK114463NIDDK NIH HHS RC2 DK118640NIH HHS DK034854Perelman School of MedicineRichard and Susan Smith Family FoundationSir Jules Thorn Charitable Trust JTA/12The New York Stem Cell FoundationUniversity of PennsylvaniaWellcome Trust 207556/Z/17/Z
Abstract
BACKGROUND AND
aimsVery early onset inflammatory bowel disease [VEOIBD] is characterized by intestinal inflammation affecting infants and children less than 6 years of age. To date, over 60 monogenic aetiologies of VEOIBD have been identified, many characterized by highly penetrant recessive or dominant variants in underlying immune and/or epithelial pathways. We sought to identify the genetic cause of VEOIBD in a subset of patients with a unique clinical presentation.
methodsWhole exome sequencing was performed on five families with ten patients who presented with a similar constellation of symptoms including medically refractory infantile-onset IBD, bilateral sensorineural hearing loss and, in the majority, recurrent infections. Genetic aetiologies of VEOIBD were assessed and Sanger sequencing was performed to confirm novel genetic findings. Western analysis on peripheral blood mononuclear cells and functional studies with epithelial cell lines were employed.
resultsIn each of the ten patients, we identified damaging heterozygous or biallelic variants in the Syntaxin-Binding Protein 3 gene [STXBP3], a protein known to regulate intracellular vesicular trafficking in the syntaxin-binding protein family of molecules, but not associated to date with either VEOIBD or sensorineural hearing loss. These mutations interfere with either intron splicing or protein stability and lead to reduced STXBP3 protein expression. Knock-down of STXBP3 in CaCo2 cells resulted in defects in cell polarity.
conclusionOverall, we describe a novel genetic syndrome and identify a critical role for STXBP3 in VEOIBD, sensorineural hearing loss and immune dysregulation.
Indexed as
Age of OnsetExome SequencingFemaleGenetic VariationHearing Loss, SensorineuralHumansImmune System DiseasesInfant, NewbornInflammatory Bowel DiseasesMaleQa-SNARE ProteinsQa-SNARE Proteinssensorineural hearing lossSTXBP3VEOIBD
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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.