Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID), Autosomal-Dominant

  • Jacob RozmusEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_45-1

Synonyms

Definition

Autosomal-dominant EDA-ID (OMIM # 612132) is an immune deficiency with ectodermal dysplasia caused by germline heterozygous gain-of-function mutations in NFKBIA which encodes IkB-alpha.

Introduction

The NF-kB signaling cascade is comprised of transcription factors that are normally sequestered in an inactive state in the cytoplasm through an association with inhibitory proteins such as IkB-alpha. Signaling through a variety of cell surface receptors involved in innate (TLRs, IL-1Rs, TNFRs) and adaptive (TCR and BCR) immunity triggers the phosphorylation of two key serine residues (S32 and S36) leading to its dissociation and subsequent proteasomal degradation. Once free from inhibition, NF-kB transcription factors are free to translocate to the nucleus and initiate cell-specific gene expression programs. Autosomal-dominant EDA-ID is associated with gain of function mutations in NFKBIAthat reduce the degradation of IkB-alpha, thus...

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References

  1. Boisson B, Puel A, Picard C, Casanova JL. Human IkBalpha gain of function: a severe and syndromic immunodeficiency. J Clin Immunol. 2017;37(5):397–412.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Courtois G, Smahi A, Reichenbach J, et al. A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest. 2003;112(7):1108–15.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Petersheim D, Massaad MJ, Lee S, et al. Mechanisms of genotype-phenotype correlation in autosomal dominant anhidrotic ectodermal dysplasia with immune deficiency. J Allergy Clin Immunol. 2017;143:1060.e3. Pii: S0091-6749(17)30984-3Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PediatricsBC Children’s Hospital and The University of British ColumbiaVancouverCanada

Section editors and affiliations

  • Stuart E. Turvey
    • 1
  1. 1.BC Children’s Hospital, Department of PediatricsUniversity of British ColumbiaVancouverCanada