The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1

Depner, Mark; Fuchs, Sebastian; Raabe, Jan; Frede, Natalie; Glocker, Cristina; Doffinger, Rainer; Gkrania-Klotsas, Effrossyni; Kumararatne, Dinakantha; Atkinson, T Prescott; Schroeder, Harry W; Niehues, Tim; Dückers, Gregor; Stray-Pedersen, Asbjørg; Baumann, Ulrich; Schmidt, Reinhold; Franco, Jose L; Orrego, Julio; Ben-Shoshan, Moshe; McCusker, Christine; Jacob, Cristina Miuki Abe; Carneiro-Sampaio, Magda; Devlin, Lisa A; Edgar, J David M; Henderson, Paul; Russell, Richard K; Skytte, Anne-Bine; Seneviratne, Suranjith L; Wanders, Jennifer; Stauss, Hans; Meyts, Isabelle; Moens, Leen; Jesenak, Milos; Kobbe, Robin; Borte, Stephan; Borte, Michael; Wright, Dowain A; Hagin, David; Torgerson, Troy R; Grimbacher, Bodo

doi:10.1007/s10875-015-0214-9

The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1

Author:

Depner, Mark

Fuchs, Sebastian ; Raabe, Jan ; Frede, Natalie ; Glocker, Cristina ; Doffinger, Rainer ; Gkrania-Klotsas, Effrossyni ; Kumararatne, Dinakantha ; Atkinson, T Prescott ; Schroeder, Harry W ; Niehues, Tim ; Dückers, Gregor ; Stray-Pedersen, Asbjørg ; Baumann, Ulrich ; Schmidt, Reinhold ; Franco, Jose L ; Orrego, Julio ; Ben-Shoshan, Moshe ; McCusker, Christine ; Jacob, Cristina Miuki Abe ; Carneiro-Sampaio, Magda ; Devlin, Lisa A ; Edgar, J David M ; Henderson, Paul ; Russell, Richard K ; Skytte, Anne-Bine ; Seneviratne, Suranjith L ; Wanders, Jennifer ; Stauss, Hans ; Meyts, Isabelle ; Moens, Leen ; Jesenak, Milos ; Kobbe, Robin ; Borte, Stephan ; Borte, Michael ; Wright, Dowain A ; Hagin, David ; Torgerson, Troy R ; Grimbacher, Bodo

Keywords:

Science & Technology, Life Sciences & Biomedicine, Immunology, Chronic mucocutaneous candidiasis, CMC, primary immunodeficiency, PID, signal transducer and activator of transcription 1, STAT1, gain-of-function, GOF, phosphorylation, HYPER-IGE SYNDROME, FUNCTION SIGNAL TRANSDUCER, DNA-BINDING DOMAIN, TH17 CELLS, IL-17 IMMUNITY, INBORN-ERRORS, T-CELLS, ACTIVATOR, DEFICIENCY, HUMANS, Adult, Candidiasis, Chronic Mucocutaneous, Cells, Cultured, Cytokines, DNA Mutational Analysis, Female, Humans, Immunologic Deficiency Syndromes, Leukocytes, Mononuclear, Male, Mutation, Pedigree, Phenotype, Protein Structure, Tertiary, STAT1 Transcription Factor, 1107 Immunology, 3204 Immunology

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.