ArticleThe Journal of allergy and clinical immunology2008
Hypomorphic nuclear factor-kappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity.
Article in The Journal of allergy and clinical immunology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 248 citations in OpenAlex.
- Monogenic etiologies of persistent human papillomavirus infections: A comprehensive systematic review.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Pooled it
- Pediatric ectodermal dysplasia with immunodeficiency caused by a hemizygousFrontiers in immunology · 2026Review
- Hyperimmunoglobulin syndromes: A review of HIGM, HIES, and HIDS.Journal of translational autoimmunity · 2025Review
- Ulcerative Lesion of the Ileocecal Region in a Patient With Immunodeficiency.Journal of gastroenterology and hepatology · 2025Article
- Evaluation of Inborn Errors of Immunity Among Patients with Opportunistic Pulmonary Infection.Clinics in chest medicine · 2025Review
- Atypical Mycobacterial Pneumonia in 2 Siblings with a Novel Hypomorphic NEMO/IKBKG Mutation.Turkish archives of pediatrics · 2024Article
- Pitfalls of genetic testing in a patient with IKBKG deficiency.Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · 2024Article
- Non-Skewed X-inactivation Results in NF-κB Essential Modulator (NEMO) Δ-exon 5-autoinflammatory Syndrome (NEMO-NDAS) in a Female with Incontinentia Pigmenti.Journal of clinical immunology · 2024Article
- Loss-of-function mutations in Keratin 32 gene disrupt skin immune homeostasis in pityriasis rubra pilaris.Nature communications · 2024Article
- Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.Inflammatory bowel diseases · 2024Review
- Monogenic Inborn Errors of Immunity with impaired IgG response to polysaccharide antigens but normal IgG levels and normal IgG response to protein antigens.Frontiers in pediatrics · 2024Review
- Elevated Serum IgA at Onset of Type 1 Diabetes in Children.Pediatric diabetes · 2024Article
- A conserved core region of the scaffold NEMO is essential for signal-induced conformational change and liquid-liquid phase separation.The Journal of biological chemistry · 2023Article
- Review
- Inborn errors of human B cell development, differentiation, and function.The Journal of experimental medicine · 2023Review
- Innate and adaptive immune abnormalities underlying autoimmune diseases: the genetic connections.Science China. Life sciences · 2023Review
- A Conserved Core Region of the Scaffold NEMO is Essential for Signal-induced Conformational Change and Liquid-liquid Phase Separation.bioRxiv : the preprint server for biology · 2023Article
- Hospitalizations for infections in primary Sjögren's syndrome patients: a nationwide incidence study.Annals of medicine · 2022Article
- Talaromyces marneffei infection associated with bronchiolitis obliterans in an HIV-negative child: a case report.BMC infectious diseases · 2022Article
- Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency.Journal of clinical immunology · 2022Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHuman hypomorphic nuclear factor-kappaB essential modulator (NEMO) mutations cause diverse clinical and immunologic phenotypes, but understanding of their scope and mechanistic links to immune function and genotype is incomplete.
objectiveWe created and analyzed a database of hypomorphic NEMO mutations to determine the spectrum of phenotypes and their associated genotypes and sought to establish a standardized NEMO reconstitution system to obtain mechanistic insights.
methodsPhenotypes of 72 individuals with NEMO mutations were compiled. NEMO L153R and C417R were investigated further in a reconstitution system. TNF-alpha or Toll-like receptor (TLR)-5 signals were evaluated for nuclear factor-kappaB activation, programmed cell death, and A20 gene expression.
resultsThirty-two different mutations were identified; 53% affect the zinc finger domain. Seventy-seven percent were associated with ectodermal dysplasia, 86% with serious pyogenic infection, 39% with mycobacterial infection, 19% with serious viral infection, and 23% with inflammatory diseases. Thirty-six percent of individuals died at a mean age of 6.4 years. CD40, IL-1, TNF-alpha, TLR, and T-cell receptor signals were impaired in 15 of 16 (94%), 6 of 7 (86%), 9 of 11 (82%), 9 of 14 (64%), and 7 of 18 (39%), respectively. Hypomorphism-reconstituted NEMO-deficient cells demonstrated partial restoration of NEMO functions. Although both L153R and C417R impaired TLR and TNF-alpha-induced NF-kappaB activation, L153R also increased TNF-alpha-induced programmed cell death with decreased A20 expression.
conclusionDistinct NEMO hypomorphs define specific disease and genetic characteristics. A reconstitution system can identify attributes of hypomorphisms independent of an individual's genetic background. Apoptosis susceptibility in L153R reconstituted cells defines a specific phenotype of this mutation that likely contributes to the excessive inflammation with which it is clinically associated.
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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.