Definition
X-linked recessive EDA-ID (OMIM # 300291) is an immune deficiency with hypohidrotic ectodermal dysplasia caused by hypomorphic hemizygous mutations in IKBKG which encodes IKK-gamma/NF-kappa-B essential modulator (NEMO).
Introduction
The NF-B signaling cascade is comprised of transcription factors that are normally sequestered in an inactive state in the cytoplasm. They are held in an inactive state through their interaction with IkB inhibitors. In response to a variety of immune and inflammatory stimuli, the IkB molecules become phosphorylated by an IkB kinase (IKK) core complex on two critical serine residues. This is a prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent proteasomal degradation. This releases the NF-kB transcription factors and allows them to translocate into the nucleus where they initiate distinct profiles of gene expression depending on the cell...
This is a preview of subscription content, log in via an institution.
References
Carrol ED, Gennery AR, Flood TJ, et al. Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO. Arch Dis Child. 2003;88(4):340–1.
Chandrakasan S, Marsh RA, Uzel G, et al. Outcome of patients with NEMO deficiency following allogeneic hematopoietic cell transplant. J Allergy Clin Immunol. 2017;139(3):1040–3.
Courtois G, Israël A. IKK regulation and human genetics. Curr Top Microbiol Immunol. 2011;349:73–95.
Döffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001;27(3):277–85.
Dupuis-Girod S, Corradini N, Hadj-Rabia S, et al. Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother. Pediatrics. 2002;109(6):e97.
Fusco F, Pescatore A, Conte MI, et al. EDA-ID and IP, two faces of the same coin: how the same IKBKG/NEMO mutation affecting the NF-kB pathway can cause immunodeficiency and/or inflammation. Int Rev Immunol. 2015;34(6):445–59.
Hubeau M, Ngadjeua F, Puel A, et al. New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein. Blood. 2011;118(4):926–35.
Israël A. The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol. 2010;2(3):a000158.
Jain A, Ma CA, Lopez-Granados E, et al. Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. J Clin Invest. 2004;114(11):1593–602.
Karaca NE, Aksu G, Ulusoy E, et al. Disseminated BCG infectious disease and hyperferritinemia in a patient with a novel NEMO mutation. J Investig Allergol Clin Immunol. 2016;26(4):268–71.
Kawai T, Nishikomori R, Heike T. Diagnosis and treatment in anhidrotic ectodermal dysplasia with immunodeficiency. Allergol Int. 2012;61(2):207–17.
Ku CL, Yang K, Bustamante J, et al. Inherited disorders of human toll-like receptor signaling: immunological implications. Immunol Rev. 2005;203:10–20.
Maubach G, Naumann M. NEMO links nuclear factor-kB to human diseases. Trends Mol Med. 2017;23(12):1138–55.
Miot C, Imai K, Imai C, et al. Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations. Blood. 2017;130(12):1456–67.
Mizukami T, Obara M, Nishikomori R, et al. Successful treatment with infliximab for inflammatory colitis in a patient with X-lined anhidrotic ectodermal dysplasia with immunodeficiency. J Clin Immunol. 2012;32(1):39–49.
Nishikomori R, Akutagawa H, Maruyama K, et al. X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival. Blood. 2004;103(12):4565–72.
Orange JS, Brodeur SR, Jain A, et al. Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest. 2002;109(11):1501–9.
Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1–S46.
Picard C, Casanova JL, Puel A. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkBalpa deficiency. Clin Microbiol Rev. 2011;24(3):490–7.
Temmerman ST, Ma CA, Borges L, et al. Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination. Blood. 2016;108(7):2324–31.
Vinolo E, Sebban H, Chaffotte A, et al. A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide and tumor necrosis factor-mediated NF-kappa B activation. J Biol Chem. 2006;281(10):6334–48.
Zonana J, Elder ME, Schneider LC, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000;67(6):1555–62.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC, part of Springer Nature
About this entry
Cite this entry
Rozmus, J. (2018). Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID), X-linked. In: MacKay, I., Rose, N. (eds) Encyclopedia of Medical Immunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9209-2_44-1
Download citation
DOI: https://doi.org/10.1007/978-1-4614-9209-2_44-1
Received:
Accepted:
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-9209-2
Online ISBN: 978-1-4614-9209-2
eBook Packages: Springer Reference MedicineReference Module Medicine