The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1
| العنوان: | The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1 |
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| المؤلفون: | Stephan Borte, Rainer Doffinger, Richard K Russell, Bodo Grimbacher, Paul Henderson, Reinhold E. Schmidt, David Hagin, Dinakantha S. Kumararatne, Robin Kobbe, Gregor Dückers, Lisa Devlin, Jan Raabe, Milos Jesenak, Sebastian Fuchs, Leen Moens, Natalie Frede, Magda Carneiro-Sampaio, Cristina Glocker, Suranjith L. Seneviratne, Hans J. Stauss, Isabelle Meyts, Ulrich Baumann, Dowain A. Wright, Christine McCusker, T. Prescott Atkinson, Troy R. Torgerson, M Depner, J Wanders, José Luis Franco, Michael Borte, Anne-Bine Skytte, Tim Niehues, J. David M. Edgar, Cristina Miuki Abe Jacob, Asbjørg Stray-Pedersen, Harry W. Schroeder, Effrossyni Gkrania-Klotsas, Moshe Ben-Shoshan, Julio César Orrego |
| المصدر: | Journal of Clinical Immunology Depner, M, Fuchs, S, Raabe, J, Frede, N, Glocker, C, Doffinger, R, Gkrania-Klotsas, E, Kumararatne, D, Atkinson, T P, Schroeder, H W, Niehues, T, Dückers, G, Stray-Pedersen, A, Baumann, U, Schmidt, R, Franco, J L, Orrego, J, Ben-Shoshan, M, McCusker, C, Jacob, C M A, Carneiro-Sampaio, M, Devlin, L A, Edgar, J D M, Henderson, P, Russell, R K, Skytte, A-B, Seneviratne, S L, Wanders, J, Stauss, H, Meyts, I, Moens, L, Jesenak, M, Kobbe, R, Borte, S, Borte, M, Wright, D A, Hagin, D, Torgerson, T R & Grimbacher, B 2016, ' The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1 ', Journal of clinical & cellular immunology, vol. 36, no. 1, pp. 73-84 . https://doi.org/10.1007/s10875-015-0214-9Test Depner, M, Fuchs, S, Raabe, J, Frede, N, Glocker, C, Doffinger, R, Gkrania-Klotsas, E, Kumararatne, D, Atkinson, T P, Schroeder, H W, Niehues, T, Dückers, G, Stray-Pedersen, A, Baumann, U, Schmidt, R, Franco, J L, Orrego, J, Ben-Shoshan, M, McCusker, C, Jacob, C M A, Carneiro-Sampaio, M, Devlin, L A, Edgar, J D M, Henderson, P, Russell, R K, Skytte, A-B, Seneviratne, S L, Wanders, J, Stauss, H, Meyts, I, Moens, L, Jesenak, M, Kobbe, R, Borte, S, Borte, M, Wright, D A, Hagin, D, Torgerson, T R & Grimbacher, B 2016, ' The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1 ', Journal of Clinical Immunology, vol. 36, no. 1, pp. 73-84 . https://doi.org/10.1007/s10875-015-0214-9Test |
| بيانات النشر: | Plenum Press, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Adult, Male, Immunology, DNA Mutational Analysis, medicine.disease_cause, primary immunodeficiency, 03 medical and health sciences, Chronic mucocutaneous candidiasis, GOF, STAT1, CMC, Medicine, Immunology and Allergy, Humans, Recurrent candida infections, Immunodeficiency, Cells, Cultured, Original Research, Mutation, gain-of-function, biology, business.industry, phosphorylation, Candidiasis, Chronic Mucocutaneous, PID, Immunologic Deficiency Syndromes, Immune dysregulation, medicine.disease, Pedigree, Protein Structure, Tertiary, 030104 developmental biology, Phenotype, STAT1 Transcription Factor, signal transducer and activator of transcription 1, Primary immunodeficiency, biology.protein, STAT protein, Leukocytes, Mononuclear, Cytokines, Female, business |
| الوصف: | PURPOSE: 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.METHODS: 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.RESULTS: 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.CONCLUSION: 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. |
| وصف الملف: | Print-Electronic; application/pdf |
| اللغة: | English |
| تدمد: | 0271-9142 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7008eda25507d6fb1c74581f93b0eaf3Test https://lirias.kuleuven.be/handle/123456789/525533Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7008eda25507d6fb1c74581f93b0eaf3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02719142 |
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