dc.contributor.author | Russell, MA | en_US |
dc.contributor.author | Pigors, M | en_US |
dc.contributor.author | Houssen, ME | en_US |
dc.contributor.author | Manson, A | en_US |
dc.contributor.author | Kelsell, D | en_US |
dc.contributor.author | Longhurst, H | en_US |
dc.contributor.author | Morgan, NG | en_US |
dc.date.accessioned | 2018-01-16T10:11:42Z | |
dc.date.available | 2017-11-17 | en_US |
dc.date.issued | 2018-02 | en_US |
dc.date.submitted | 2017-12-07T12:25:23.946Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/31330 | |
dc.description.abstract | Common variable immunodeficiency (CVID) is characterised by repeated infection associated with primary acquired hypogammaglobulinemia. CVID frequently has a complex aetiology but, in certain cases, it has a monogenic cause. Recently, variants within the gene encoding the transcription factor STAT3 were implicated in monogenic CVID. Here, we describe a patient presenting with symptoms synonymous with CVID, who displayed reduced levels of IgG and IgA, repeated viral infections and multiple additional co-morbidities. Whole-exome sequencing revealed a de novo novel missense mutation in the coiled-coil domain of STAT3 (c.870A>T; p.K290N). Accordingly, the K290N variant of STAT3 was generated, and a STAT3 responsive dual-luciferase reporter assay revealed that the variant strongly enhances STAT3 transcriptional activity both under basal and stimulated (with IL-6) conditions. Overall, these data complement earlier studies in which CVID-associated STAT3 mutations are predicted to enhance transcriptional activity, suggesting that such patients may respond favourably to IL-6 receptor antagonists (e.g. tocilizumab). | en_US |
dc.description.sponsorship | We gratefully acknowledge the Mission Sector of the Egyptian Ministry of Higher Education (Arab Republic of Egypt) who provided funding for Maha E. Houssen to work as a visiting postdoctoral fellow at the University of Exeter (March 2016–September 2016). This work was also supported by Diabetes UK (grant: 15/0005156). | en_US |
dc.format.extent | 132 - 136 | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Clin Immunol | en_US |
dc.rights | © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | CVID | en_US |
dc.subject | Common variable immunodeficiency | en_US |
dc.subject | Hypogammaglobulinemia | en_US |
dc.subject | STAT3 | en_US |
dc.subject | Whole exome sequencing | en_US |
dc.title | A novel de novo activating mutation in STAT3 identified in a patient with common variable immunodeficiency (CVID). | en_US |
dc.type | Article | |
dc.rights.holder | © 2017 Elsevier Inc. All rights reserved. | |
dc.identifier.doi | 10.1016/j.clim.2017.11.007 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29180260 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 187 | en_US |
dcterms.dateAccepted | 2017-11-17 | en_US |