| Title |
The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1
|
|---|---|
| Published in |
Journal of Clinical Immunology, November 2015
|
| DOI | 10.1007/s10875-015-0214-9 |
| Pubmed ID | |
| Authors |
Mark Depner, Sebastian Fuchs, Jan Raabe, Natalie Frede, Cristina Glocker, Rainer Doffinger, Effrossyni Gkrania-Klotsas, Dinakantha Kumararatne, T. Prescott Atkinson, Harry W. Schroeder, Tim Niehues, Gregor Dückers, Asbjørg Stray-Pedersen, Ulrich Baumann, Reinhold Schmidt, Jose L. Franco, Julio Orrego, Moshe Ben-Shoshan, Christine McCusker, Cristina Miuki Abe Jacob, Magda Carneiro-Sampaio, Lisa A. Devlin, J. David M. Edgar, Paul Henderson, Richard K. Russell, Anne-Bine Skytte, Suranjith L. Seneviratne, Jennifer Wanders, Hans Stauss, Isabelle Meyts, Leen Moens, Milos Jesenak, Robin Kobbe, Stephan Borte, Michael Borte, Dowain A. Wright, David Hagin, Troy R. Torgerson, Bodo Grimbacher |
| Abstract |
Gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) result in unbalanced STAT signaling and cause immune dysregulation and immunodeficiency. The latter is often characterized by the susceptibility to recurrent Candida infections, resulting in the clinical picture of chronic mucocutaneous candidiasis (CMC). This study aims to assess the frequency of GOF STAT1 mutations in a large international cohort of CMC patients. STAT1 was sequenced in genomic DNA from 57 CMC patients and 35 healthy family members. The functional relevance of nine different STAT1 variants was shown by flow cytometric analysis of STAT1 phosphorylation in patients' peripheral blood cells (PBMC) after stimulation with interferon (IFN)-α, IFN-γ or interleukin-27 respectively. Extended clinical data sets were collected and summarized for 26 patients. Heterozygous mutations within STAT1 were identified in 35 of 57 CMC patients (61 %). Out of 39 familial cases from 11 families, 26 patients (67 %) from 9 families and out of 18 sporadic cases, 9 patients (50 %) were shown to have heterozygous mutations within STAT1. Thirteen distinct STAT1 mutations are reported in this paper. Eight of these mutations are known to cause CMC (p.M202V, p.A267V, p.R274W, p.R274Q, p.T385M, p.K388E, p.N397D, and p.F404Y). However, five STAT1 variants (p.F172L, p.Y287D, p.P293S, p.T385K and p.S466R) have not been reported before in CMC patients. STAT1 mutations are frequently observed in patients suffering from CMC. Thus, sequence analysis of STAT1 in CMC patients is advised. Measurement of IFN- or IL-induced STAT1 phosphorylation in PBMC provides a fast and reliable diagnostic tool and should be carried out in addition to genetic testing. |
Mendeley readers
The data shown below were compiled from readership statistics for 119 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Denmark | 1 | <1% |
| Italy | 1 | <1% |
| Unknown | 117 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 16 | 13% |
| Student > Bachelor | 16 | 13% |
| Researcher | 15 | 13% |
| Student > Master | 15 | 13% |
| Other | 12 | 10% |
| Other | 24 | 20% |
| Unknown | 21 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 38 | 32% |
| Biochemistry, Genetics and Molecular Biology | 22 | 18% |
| Immunology and Microbiology | 18 | 15% |
| Agricultural and Biological Sciences | 11 | 9% |
| Computer Science | 1 | <1% |
| Other | 4 | 3% |
| Unknown | 25 | 21% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 November 2015.
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#20,298,249
of 22,835,198 outputs
Outputs from Journal of Clinical Immunology
#1,256
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Outputs of similar age from Journal of Clinical Immunology
#16
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