A Novel Gain-of-Function IKBA Mutation Underlies Ectodermal Dysplasia with Immunodeficiency and Polyendocrinopathy

Schimke, Lena F.; Rieber, Nikolaus; Rylaarsdam, Stacey; Cabral-Marques, Otávio; Hubbard, Nicholas; Puel, Anne; Kallmann, Laura; Sombke, Stephanie Anover; Notheis, Gundula; Schwarz, Hans; Kammer, Birgit; Hökfelt, Tomas; Repp, Reinald; Pïcard, Capucine; Casanova, Jean‐Laurent; Belohradsky, Bernd H.; Albert, Michael H.; Ochs, Hans D.; Renner, Ellen D.; Torgerson, Troy R.

doi:10.1007/s10875-013-9906-1

Cited by 61 publications

(36 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Between the years 2003 and 2015, reports of 7 patients with AD-EDA-ID who underwent HSCT were published (Courtois et al 2003;Janssen et al 2004;Dupuis-Girod et al 2006;Lopez-Granados et al 2008;Fish et al 2009;Wu et al 2010;Schimke et al 2013;Yoshioka et al 2013;Scarselli et al 2015). A summary of patient characteristics can be found in Table 3.…”

Section: Autosomal Dominant Ectodermal Dysplasia With Immunodeficiencymentioning

confidence: 99%

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Scott

Grunebaum

2017

LymphoSign Journal

View full text Add to dashboard Cite

The nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) family of transcription factors plays an instrumental role in human immunity and lymphoid organ development. Inherited defects affecting these factors or their regulation are associated with increased susceptibility to infections, as well as non-immune abnormalities. Hematopoietic stem cell transplantations (HSCT) have been shown to correct the immune abnormalities in a few patients with NFκB pathway defects. Here we review the pre-HSCT characteristics, as well as the HSCT and outcome of 35 patients who received HSCT for NFκB defects. Twenty-three patients (65.7%) were reported to have survived HSCT. Survival was higher among patients with X-linked ectodermal dysplasia and immunodeficiency (XL-EDA-ID), and those with CARD11-BCL10-MALT1 (CBM) complex defects, in comparison to patients with autosomal dominant ectodermal dysplasia and immunodeficiency (AD-EDA-ID) and IKBKB defects. Survival following myeloablative conditioning was similar to that after reduced intensity conditioning, although donor cells engraftment and immune reconstitution after HSCT was not complete in some patients. The effects of HSCT on organ dysfunction associated with NFκB defects, such as liver toxicity or bowel inflammation, are still not clear. Earlier identification and transplantation of affected patients, as well as better understanding of the pathogenesis and complications of the different NFκB mutations, might improve outcome of HSCT for specific patient populations. Statement of novelty:This review highlights the current indications, regimens, and outcome of HSCT for inherited defects involving various components of the canonical and non-canonical NFκB pathways.

show abstract

Section: Autosomal Dominant Ectodermal Dysplasia With Immunodeficiencymentioning

confidence: 99%

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Scott

Grunebaum

2017

LymphoSign Journal

View full text Add to dashboard Cite

show abstract

“…Patients with EDA-ID as a result of either NEMO or IKBA mutations develop invasive pyogenic bacterial infections. With regard to fungal disease, patients with IKBA mutations are universally affected by CMC and 60% of them develop PCP (Picard et al 2011); decreased numbers of IL-17 þ T cells have been reported in these patients (Schimke et al 2013). Instead, CMC and PCP are far less common in NEMO-deficient patients (,10%) (Salt et al 2008;Picard et al 2011).…”

Section: Anhidrotic Ectodermal Dysplasia With Immunodeficiency (Eda-id)mentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

View full text Add to dashboard Cite

Correspondence: lionakism@niaid.nih.gov A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens.

show abstract

“…Autoimmune or autoinflammatory diseases have been previously observed in patients with NEMO deficiency [8]. Previous studies in patients with NFKB2 [9] and IKBA [10] deficiencies who developed alopecia totalis, tranchyonychia, psoriasiform dermatitis, and polyendocrinopathy indicate the important role of noncanonical and canonical NF-κB-pathways in the Fig. 1.…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 86%

Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura

Ramírez-Alejo

Alcántara-Montiel

Yamazaki‐Nakashimada³

et al. 2015

Clinical Immunology

View full text Add to dashboard Cite

A Novel Gain-of-Function IKBA Mutation Underlies Ectodermal Dysplasia with Immunodeficiency and Polyendocrinopathy

Abstract: The novel heterozygous mutation p.M37K in IκB-α impairs NF-κB activation causing autosomal dominant EDA-ID with an expanded clinical phenotype.

Cited by 61 publications

References 52 publications

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Hematopoietic stem cell transplantations for primary immune deficiencies associated with NFκB mutations: A review of the literature

Mendelian Genetics of Human Susceptibility to Fungal Infection

Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura

Contact Info

Product

Resources

About