Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura
Copyright © 2015 Elsevier Inc. All rights reserved.
| Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 160(2015), 2 vom: 01. Okt., Seite 163-71 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , , , , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2015
|
| Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Ectodermal dysplasia Immune thrombocytopenic purpura Immunodeficiency NEMO IKBKG protein, human I-kappa B Kinase EC 2.7.11.10 |
| Zusammenfassung: | Copyright © 2015 Elsevier Inc. All rights reserved. NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females |
|---|---|
| Beschreibung: | Date Completed 15.12.2015 Date Revised 24.09.2015 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2015.06.007 |