ArticleThe Journal of allergy and clinical immunology2018
Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency.
Article in The Journal of allergy and clinical immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Article
- Monogenic disorders of the TNF signalling pathway.Nature reviews. Rheumatology · 2026Review
- A Novel De NovoGenes · 2022Article
- Ectodysplasin A (EDA) Signaling: From Skin Appendage to Multiple Diseases.International journal of molecular sciences · 2022Review
- A heterozygous N-terminal truncation mutation ofGenes & diseases · 2022Article
- EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity.Bone marrow transplantation · 2021Review
- Review
- Dominant-negative NFKBIA mutation promotes IL-1β production causing hepatic disease with severe immunodeficiency.The Journal of clinical investigation · 2020Article
- A 23-Year Follow-Up of a Patient with Gain-of-Function IkB-Alpha Mutation and Stable Full Chimerism After Hematopoietic Stem Cell Transplantation.Journal of clinical immunology · 2020Article
- Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-κB-inducing kinase deficiency.The Journal of allergy and clinical immunology · 2019Article
- A novel 14q13.1-21.1 deletion identified by CNV-Seq in a patient with brain-lung-thyroid syndrome, tooth agenesis and immunodeficiency.Molecular cytogenetics · 2019Article
- IKBA S32 Mutations Underlie Ectodermal Dysplasia with Immunodeficiency and Severe Noninfectious Systemic Inflammation.Journal of clinical immunology · 2018Article
- Role of the NFκB-signaling pathway in cancer.OncoTargets and therapy · 2018Review
- Clinical and Genetic Characteristics of Ectodermal Dysplasia in Four Indian Children.Indian journal of dermatologyArticle
Corrections and comments
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Authors and funding
24 authors at 15 institutions in 7 countries.
Funding
Abstract
backgroundAutosomal dominant anhidrotic ectodermal dysplasia with immune deficiency (AD EDA-ID) is caused by heterozygous point mutations at or close to serine 32 and serine 36 or N-terminal truncations in IκBα that impair its phosphorylation and degradation and thus activation of the canonical nuclear factor κ light chain enhancer of activated B cells (NF-κB) pathway. The outcome of hematopoietic stem cell transplantation is poor in patients with AD EDA-ID despite achievement of chimerism. Mice heterozygous for the serine 32I mutation in IκBα have impaired noncanonical NF-κB activity and defective lymphorganogenesis.
objectiveWe sought to establish genotype-phenotype correlation in patients with AD EDA-ID.
methodsA disease severity scoring system was devised. Stability of IκBα mutants was examined in transfected cells. Immunologic, biochemical, and gene expression analyses were performed to evaluate canonical and noncanonical NF-κB signaling in skin-derived fibroblasts.
resultsDisease severity was greater in patients with IκBα point mutations than in those with truncation mutations. IκBα point mutants were expressed at significantly higher levels in transfectants compared with truncation mutants. Canonical NF-κB-dependent IL-6 secretion and upregulation of the NF-κB subunit 2/p100 and RELB proto-oncogene, NF-κB subunit (RelB) components of the noncanonical NF-κB pathway were diminished significantly more in patients with point mutations compared with those with truncations. Noncanonical NF-κB-driven generation of the transcriptionally active p100 cleavage product p52 and upregulation of CCL20, intercellular adhesion molecule 1 (ICAM1), and vascular cell adhesion molecule 1 (VCAM1), which are important for lymphorganogenesis, were diminished significantly more in LPS plus α-lymphotoxin β receptor-stimulated fibroblasts from patients with point mutations compared with those with truncations.
conclusionsIκBα point mutants accumulate at higher levels compared with truncation mutants and are associated with more severe disease and greater impairment of canonical and noncanonical NF-κB activity in patients with AD EDA-ID.
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