Evidence map›Paper›PMID 32084423›Full record

ArticleGastroenterology2020

Prevalence and Clinical Features of Inflammatory Bowel Diseases Associated With Monogenic Variants, Identified by Whole-Exome Sequencing in 1000 Children at a Single Center.

Eileen Crowley, Neil Warner, Jie Pan, Sam Khalouei, Abdul Elkadri, Karoline Fiedler, Justin Foong, Andrei L Turinsky, Dana Bronte-Tinkew, Shiqi Zhang and 21 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Gastroenterology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06986382 (Phase 1b/2a Trial of Allogeneic Hematopoietic Stem Cell Transplantation), which is not on this map. Cited by 75 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 8 pooled it
6.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

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.

2 · The registry

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.

NCT06986382 phase1 / phase2not yet recruitingnot on this mapstarted 2025, after this paper: background citation

Phase 1b/2a Trial of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) From an HLA-partially Matched Related or Unrelated Donor After TCRab+ T-cell/CD19+ B-cell Depletion for Patients With Monogenic and/or Early-onset (EO), Medically Refractory (MR) Crohn Disease (CD)

TypeinterventionalSponsorStanford UniversityRan2025 to 2040Enrolled14ConditionsCrohn DiseaseArmsCliniMACS® TCR α/β Reagent Kit and CliniMACS® CD19 System, Prednisone/Methylprenisolone, Palifermin, ATG, Clofarabine
3 · Its place in the literature

Who cites it

75 citing papers in PubMed, 8 syntheses or guidelines pooled it, 113 citations in OpenAlex.

  1. Pooled it
  2. Red flags to suspect inborn errors of immunity in patients with autoimmune diseasesBiomedica : revista del Instituto Nacional de Salud · 2024
    Pooled it
  3. Pooled it
  4. A Systematic Review of Monogenic Inflammatory Bowel Disease.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2022
    Pooled it
  5. Crohn's-like Enteritis in X-Linked Agammaglobulinemia: A Case Series and Systematic Review.The journal of allergy and clinical immunology. In practice · 2021
    Pooled it
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  20. Monogenic inflammatory bowel disease: An unfolding enigma.World journal of clinical pediatrics · 2025
    Review

15 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

31 authors at 10 institutions in 5 countries.

Eileen CrowleySickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada; School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland; Division of Pediatric Gastroenterology, Western University, Children's Hospital, London Health Sciences Centre, London, Ontario, Canada.
Neil WarnerSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jie PanSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Sam KhaloueiCentre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Abdul ElkadriSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada; Division of Pediatric Gastroenterology, Medical College of Wisconsin, Milwaukee, Wisconsin.
Karoline FiedlerSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Justin FoongCentre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Andrei L TurinskyCentre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Dana Bronte-TinkewSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Shiqi ZhangSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Jamie HuSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
David TianSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Dalin LiF. Widjaja Foundation Inflammatory Bowel Disease Center and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles, California.
Julie HorowitzRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, New York.
Iram SiddiquiDivision of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Julia UptonDivision of Immunology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Chaim M RoifmanDivision of Immunology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Peter C ChurchSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Donna A WallBlood and Marrow Transplant/Cellular Therapy, Haematology/Oncology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
Arun K RamaniCentre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Daniel KotlarzDr von Hauner Children's Hospital, Department of Pediatrics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
Christoph KleinDr von Hauner Children's Hospital, Department of Pediatrics, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany.
Holm UhligTranslational Gastroenterology Unit, University of Oxford, UK; Department of Pediatrics, University of Oxford, UK.
Scott B SnapperDivision of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts.
Claudia Gonzaga-JaureguiRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, New York.
Andrew D PatersonDalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Dermot P B McGovernF. Widjaja Foundation Inflammatory Bowel Disease Center and Immunobiology Research Institute at Cedars-Sinai Medical Center, Los Angeles, California.
Michael BrudnoCentre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.
Thomas D WaltersSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Anne M GriffithsSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada.
Aleixo M MuiseSickKids Inflammatory Bowel Disease Center, The Hospital for Sick Children, Toronto, Ontario, Canada; Cell Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatrics, Institute of Medical Science and Biochemistry, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: aleixo.muise@utoronto.ca.
SickKids Foundation · CAUniversity of Toronto · CAHospital for Sick Children · CACedars-Sinai Medical Center · USLudwig-Maximilians-Universität München · DERegeneron (United States) · USBrigham and Women's Hospital · USChildren's Hospital of Wisconsin · USUniversity College Dublin · IEUniversity of Oxford · GB

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
Using polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1992 to 2020
$31.1M
COngenital Diarrhea and Enteropathy (PediCODE) Consortium and BioRepositoryRC2DK118640 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI James Richard Goldenring, Izumi Kaji · 2019 to 2026
$14.8M
Utilizing the Phenomics of IBD to Enhance Gene DiscoveryU01DK062413 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI Dermot Patrick McGovern · 2002 to 2026
$12.2M
CIHRNIDDK NIH HHS P01 DK046763NIDDK NIH HHS P30 DK034854NIDDK NIH HHS RC2 DK118640NIDDK NIH HHS U01 DK062413
6 · The paper itself

Abstract

BACKGROUND &

aimsA proportion of infants and young children with inflammatory bowel diseases (IBDs) have subtypes associated with a single gene variant (monogenic IBD). We aimed to determine the prevalence of monogenic disease in a cohort of pediatric patients with IBD.

methodsWe performed whole-exome sequencing analyses of blood samples from an unselected cohort of 1005 children with IBD, aged 0-18 years (median age at diagnosis, 11.96 years) at a single center in Canada and their family members (2305 samples total). Variants believed to cause IBD were validated using Sanger sequencing. Biopsies from patients were analyzed by immunofluorescence and histochemical analyses.

resultsWe identified 40 rare variants associated with 21 monogenic genes among 31 of the 1005 children with IBD (including 5 variants in XIAP, 3 in DOCK8, and 2 each in FOXP3, GUCY2C, and LRBA). These variants occurred in 7.8% of children younger than 6 years and 2.3% of children aged 6-18 years. Of the 17 patients with monogenic Crohn's disease, 35% had abdominal pain, 24% had nonbloody loose stool, 18% had vomiting, 18% had weight loss, and 5% had intermittent bloody loose stool. The 14 patients with monogenic ulcerative colitis or IBD-unclassified received their diagnosis at a younger age, and their most predominant feature was bloody loose stool (78%). Features associated with monogenic IBD, compared to cases of IBD not associated with a single variant, were age of onset younger than 2 years (odds ratio [OR], 6.30; P = .020), family history of autoimmune disease (OR, 5.12; P = .002), extra-intestinal manifestations (OR, 15.36; P < .0001), and surgery (OR, 3.42; P = .042). Seventeen patients had variants in genes that could be corrected with allogeneic hematopoietic stem cell transplantation.

conclusionsIn whole-exome sequencing analyses of more than 1000 children with IBD at a single center, we found that 3% had rare variants in genes previously associated with pediatric IBD. These were associated with different IBD phenotypes, and 1% of the patients had variants that could be potentially corrected with allogeneic hematopoietic stem cell transplantation. Monogenic IBD is rare, but should be considered in analysis of all patients with pediatric onset of IBD.

Indexed as

Exome SequencingGenetic VariationAdolescentAge FactorsBiological ProductsChildChild, PreschoolColitis, UlcerativeCrohn DiseaseFemaleGenetic Predisposition to DiseaseHematopoietic Stem Cell TransplantationHumansInfantInfant, NewbornMaleBiological ProductsGeneticsHSCTPrevalenceRisk Factor

Identifiers

PMID32084423
PMCPMC7283012
OpenAlexW3007865891

What OpenQuestion holds

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Registered trials

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.