TNFAIP3 haploinsufficiency is the cause of autoinflammatory manifestations in a patient with a deletion of 13Mb on chromosome 6

TNFAIP3 haploinsufficiency is the cause of autoinflammatory manifestations in a patient with a deletion of 13Mb on chromosome 6

Copyright © 2018 Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 191(2018) vom: 15. Juni, Seite 44-51
1. Verfasser: Franco-Jarava, Clara (VerfasserIn)
Weitere Verfasser: Wang, Hongying, Martin-Nalda, Andrea, Alvarez, de la Sierra Daniel, García-Prat, Marina, Bodet, Domingo, García-Patos, Vicenç, Plaja, Alberto, Rudilla, Francesc, Rodriguez-Sureda, Victor, García-Latorre, Laura, Aksentijevich, Ivona, Colobran, Roger, Soler-Palacín, Pere
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Case Reports Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Autoinflammatory diseases Behçet’s disease Chromosome deletion Comparative Genomic Hybridization (CGH) Oral ulcer TNFAIP3 mehr... NF-kappa B TNFAIP3 protein, human EC 3.4.19.12 Tumor Necrosis Factor alpha-Induced Protein 3
Beschreibung
Zusammenfassung:Copyright © 2018 Elsevier Inc. All rights reserved.
There is scarce literature about autoinflammation in syndromic patients. We describe a patient who, in addition to psychomotor and growth delay, presented with fevers, neutrophilic dermatosis, and recurrent orogenital ulcers. Comparative Genomic Hybridization (CGH) array permitted to identify a 13.13Mb deletion on chromosome 6, encompassing 53 genes, and including TNFAIP3 gene (A20). A20 is a potent inhibitor of the NF-kB signalling pathway and restricts inflammation via its deubiquitinase activity. Western blotting and immunoprecipitation assays showed decreased A20 expression and increased phosphorylation of p65 and IkBa. Patient's cells displayed increased levels of total K63-linked ubiquitin and increased levels of ubiquitinated RIP and NEMO after stimulation with TNF. We describe the molecular characterization of an autoinflammatory disease due to a large chromosomal deletion and review the phenotypes of patients with A20 haploinsufficiency. CGH arrays should be the first diagnostic method for comprehensive analysis of patients with syndromic features and immune dysregulation
Beschreibung:Date Completed 05.07.2019
Date Revised 05.07.2019
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2018.03.009