ArticleJournal of clinical immunology2013
A novel gain-of-function IKBA mutation underlies ectodermal dysplasia with immunodeficiency and polyendocrinopathy.
Article in Journal of clinical immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 61 citations in OpenAlex.
- Fungal Infections in Disorders of Inborn Errors of Immunity.Clinical reviews in allergy & immunology · 2026Review
- Article
- γδ T Cells and Inborn Errors of Immunity.European journal of immunology · 2025Review
- NFκB pathway dysregulation due to reduced RelB expression leads to severe autoimmune disorders and declining immunity.Journal of autoimmunity · 2023Article
- A Novel De NovoGenes · 2022Article
- A heterozygous N-terminal truncation mutation ofGenes & diseases · 2022Article
- Review
- Dominant-negative NFKBIA mutation promotes IL-1β production causing hepatic disease with severe immunodeficiency.The Journal of clinical investigation · 2020Article
- Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study.Signal transduction and targeted therapy · 2020Review
- T Cell Impairment Is Predictive for a Severe Clinical Course in NEMO Deficiency.Journal of clinical immunology · 2020Article
- Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation.Frontiers in immunology · 2019Review
- Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency.The Journal of allergy and clinical immunology · 2018Article
- Transcriptome of Porcine PBMCs over Two Generations Reveals Key Genes and Pathways Associated with Variable Antibody Responses post PRRSV Vaccination.Scientific reports · 2018Article
- Nuclear Factor-kappaB in Autoimmunity: Man and Mouse.Frontiers in immunology · 2018Review
- Article
- Human IκBα Gain of Function: a Severe and Syndromic Immunodeficiency.Journal of clinical immunology · 2017Review
- Review
- Autoimmunity and Primary Immunodeficiency Disorders.Journal of clinical immunology · 2016Review
- Gain-of-function mutations and immunodeficiency: at a loss for proper tuning of lymphocyte signaling.Current opinion in allergy and clinical immunology · 2015Review
- Rare mendelian primary immunodeficiency diseases associated with impaired NF-κB signaling.Genes and immunity · 2015Review
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis study reports the identification of a novel heterozygous IKBA missense mutation (p.M37K) in a boy presenting with ectodermal dysplasia with immunodeficiency (EDA-ID) who had wild type IKBKG gene encoding NEMO. Our aim was to characterize the clinical course of this IκB-α gain-of-function mutant and to investigate if the p.M37K substitution affects NF-κB activation by interfering with IκB-α degradation, thus impairing NF-κB signaling and causing the EDA-ID phenotype.
methodsNF-κB signaling was evaluated by measuring IκB-α degradation in patient fibroblasts. In addition, transiently transfected HeLa cells expressing either the M37K-mutant IκB-α allele, the previously characterized S36A-mutant IκB-α allele, or wild type IκB-α were evaluated for IκB-α degradation and NF-κB nuclear translocation following stimulation with TNF-α.
resultsClinical findings revealed a classical ectodermal dysplasia phenotype complicated by recurrent mucocutaneous candidiasis, hypothyroidism, hypopituitarism, and profound combined immunodeficiency with decreased numbers of IL-17 T cells. IκB-α degradation after TNF-α and TLR agonist stimulation was abolished in patient fibroblasts as well as in HeLa cells expressing M37K-IκB-α similar to cells expressing S36A-IκB-α resulting in impaired nuclear translocation of NF-κB and reduced NF-κB dependent luciferase activity compared to cells expressing wild type IκB-α. Patient whole blood cells failed to secrete IL-6 in response to IL-1ß, Pam2CSK4, showed reduced responses to LPS and PMA/Ionomycin, and lacked IL-10 production in response to TNF-α.
conclusionThe novel heterozygous mutation p.M37K in IκB-α impairs NF-κB activation causing autosomal dominant EDA-ID with an expanded clinical phenotype.
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