ArticleThe Journal of allergy and clinical immunology2022
Molecular diagnosis of childhood immune dysregulation, polyendocrinopathy, and enteropathy, and implications for clinical management.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
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Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.
- Italian pediatric experts' consensus statement on diagnosis and management of primary atopic disorders.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2025Guideline
- BCL11B-related disease: a single phenotypic entity?European journal of human genetics : EJHG · 2025Pooled it
- Management change following NGS diagnosis of inborn errors of immunity: The Australasian experience.Journal of human immunity · 2026Article
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- Evolving epigenomics of immune cells at single-nucleus resolution in children en route to type 1 diabetes.Nature communications · 2026Article
- Immunocyte phenotypes and childhood disease susceptibility: insights from bidirectional Mendelian randomization and implications for immunomodulatory therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A TOM1 variant impairs interaction with TOLLIP, autophagosome-lysosome fusion and regulation of innate immunity.Disease models & mechanisms · 2025Article
- T and NK cell functionality in a patient harboring heterozygous novel BCL11B p.Asp632fsAla∗91 and STX11 p.R129P mutations.Heliyon · 2025Article
- Regional patterns of genetic variants in expanded carrier screening: a next-generation sequencing pilot study in Fujian Province, China.Frontiers in genetics · 2025Article
- IRF2BP2 binds to a conserved RxSVI motif of protein partners and regulates megakaryocytic differentiation.Nature communications · 2024Article
- 2q33 Deletions Underlying Syndromic and Non-syndromic CTLA4 Deficiency.Journal of clinical immunology · 2024Article
- Review
- Further validation of craniosynostosis as a part of phenotypic spectrum of BCL11B-related BAFopathy.American journal of medical genetics. Part A · 2023Article
- Dysregulated IFN-γ signals promote autoimmunity in STAT1 gain-of-function syndrome.Science translational medicine · 2023Article
- The genetics of monogenic intestinal epithelial disorders.Human genetics · 2023Review
- Case Report: A novel IRF2BP2 mutation in an IEI patient with recurrent infections and autoimmune disorders.Frontiers in immunology · 2023Article
- Novel frameshift variants expand the map of the genetic defects in IRF2BP2.Frontiers in immunology · 2023Article
- Chromosomal microarray analysis supplements exome sequencing to diagnose children with suspected inborn errors of immunity.Frontiers in immunology · 2023Article
- The role of the CBM complex in allergic inflammation and disease.The Journal of allergy and clinical immunology · 2022Review
- Expanding spectrum, intrafamilial diversity, and therapeutic challenges from 15 patients with heterozygous CARD11-associated diseases: A single center experience.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMost patients with childhood-onset immune dysregulation, polyendocrinopathy, and enteropathy have no genetic diagnosis for their illness. These patients may undergo empirical immunosuppressive treatment with highly variable outcomes.
objectiveWe sought to determine the genetic basis of disease in patients referred with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like (IPEX-like) disease, but with no mutation in FOXP3; then to assess consequences of genetic diagnoses for clinical management.
methodsGenomic DNA was sequenced using a panel of 462 genes implicated in inborn errors of immunity. Candidate mutations were characterized by genomic, transcriptional, and (for some) protein analysis.
resultsOf 123 patients with FOXP3-negative IPEX-like disease, 48 (39%) carried damaging germline mutations in 1 of the following 27 genes: AIRE, BACH2, BCL11B, CARD11, CARD14, CTLA4, IRF2BP2, ITCH, JAK1, KMT2D, LRBA, MYO5B, NFKB1, NLRC4, POLA1, POMP, RAG1, SH2D1A, SKIV2L, STAT1, STAT3, TNFAIP3, TNFRSF6/FAS, TNRSF13B/TACI, TOM1, TTC37, and XIAP. Many of these genes had not been previously associated with an IPEX-like diagnosis. For 42 of the 48 patients with genetic diagnoses, knowing the critical gene could have altered therapeutic management, including recommendations for targeted treatments and for or against hematopoietic cell transplantation.
conclusionsMany childhood disorders now bundled as "IPEX-like" disease are caused by individually rare, severe mutations in immune regulation genes. Most genetic diagnoses of these conditions yield clinically actionable findings. Barriers are lack of testing or lack of repeat testing if older technologies failed to provide a diagnosis.
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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 OpenQuestion graph.