A novel NFKBIA variant substituting serine 36 of IκBα causes immunodeficiency with warts, bronchiectasis and juvenile rheumatoid arthritis in the absence of ectodermal dysplasia

A novel NFKBIA variant substituting serine 36 of IκBα causes immunodeficiency with warts, bronchiectasis and juvenile rheumatoid arthritis in the absence of ectodermal dysplasia

Copyright © 2019 Elsevier Inc. All rights reserved.

Détails bibliographiques
Publié dans:Clinical immunology (Orlando, Fla.). - 1999. - 210(2020) vom: 15. Jan., Seite 108269
Auteur principal: Sogkas, Georgios (Auteur)
Autres auteurs: Adriawan, Ignatius R, Ringshausen, Felix C, Baumann, Ulrich, Schröder, Claudia, Klemann, Christian, von Hardenberg, Sandra, Schmidt, Gunnar, Bernd, Auber, Jablonka, Alexandra, Ernst, Diana, Schmidt, Reinhold E, Atschekzei, Faranaz
Format: Article en ligne
Langue:English
Publié: 2020
Accès à la collection:Clinical immunology (Orlando, Fla.)
Sujets:Case Reports Journal Article Research Support, Non-U.S. Gov't Arthritis Bronchiectasis Monogenic immunodeficiency NFKBIA Specific antibody deficiency Warts Gentamicins plus... NFKBIA protein, human NF-KappaB Inhibitor alpha 139874-52-5 Azithromycin 83905-01-5
Description
Résumé:Copyright © 2019 Elsevier Inc. All rights reserved.
Genetic studies have led to identification of an increasing number of monogenic primary immunodeficiency disorders. Monoallelic pathogenic gain-of-function (GOF) variants in NFKBIA, the gene encoding IκBα, result in an immunodeficiency disorder, typically accompanied by anhidrotic ectodermal dysplasia (EDA). So far, 14 patients with immunodeficiency due to NFKBIA GOF mutations have been reported. In this study we report three patients from the same family with immunodeficiency, presenting with recurrent respiratory tract infections, bronchiectasis and viral skin conditions due to a novel pathogenic NFKBIA variant (c.106 T > G, p.Ser36Ala), which results in reduced IκBα degradation. Immunological investigations revealed inadequate antibody responses against vaccine antigens, despite hypergammaglobulinemia. Interestingly, none of the studied patients displayed features of EDA. Therefore, missense NFKBIA variants substituting serine 36 of IκBα, differ from the rest of pathogenic GOF NFKBIA variants in that they cause combined immunodeficiency, even in the absence of EDA
Description:Date Completed 31.07.2020
Date Revised 31.07.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2019.108269