1. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype
- Author
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Toubiana, J., Okada, S., Hiller, J., Oleastro, M., Lagos Gomez, M., Aldave Becerra, J. C., Ouachee-Chardin, M., Fouyssac, F., Girisha, K. M., Etzioni, A., Van Montfrans, J., Camcioglu, Y., Kerns, L. A., Belohradsky, B., Blanche, S., Bousfiha, A., Rodriguez-Gallego, C., Meyts, I., Kisand, K., Reichenbach, J., Renner, E. D., Rosenzweig, S., Grimbacher, B., van de Veerdonk, F. L., Traidl-Hoffmann, C., Picard, C., Marodi, L., Morio, T., Kobayashi, M., Lilic, D., Milner, J. D., Holland, S., Casanova, J. -L., Puel A, Cypowyj S, Thumerelle C, Toulon A, Bustamante J, Tahuil N, SALHI, DALILA, Boiu S, Chopra C, Di Giovanni D, Bezrodnik L, Boutros J, Thomas C, Lacuesta G, Jannier S, Korganow AS, Paillard C, Boutboul, Bué M, Marie-Cardine A, Bayart S, Migaud M, Weiss, Karmochkine M, Garcia-Martinez JM, Stephan JL, Bensaid P, Jeannoel GP, Witte T, Baumann U, Harrer T, Navarrete C, ACOSTA HUGHES, BENJAMIN, Firinu, Pignata C, Picco P, Mendoza D, Lugo Reyes SO, Torres Lozano C, Ortega-Cisneros M, Cortina M, Mesdaghi M, Nabavi M, Español T, Martínez-Saavedra MT, Rezaei N, Zoghi S, Pac M, Barlogis V, Revon-Rivière G, Haimi-Cohen Y, Spiegel R, Miron D, Bouchaib J, Blancas-Galicia L, Toth B, Drexel B, Rohrlich PS, Lesens O, Hoernes M, Drewe E, Abinum M, Sawalle-Belohradsky J, Kindle G, Depner M, Milani L, Nikopensius T, Remm M, Talas UG, Tucker M, Willis M, Leonard S, Meuwissen H, Ferdman RM, CORBO UGULINO, WALLACE, Desai MM, Taur P, Badolato R, Soltesz B, Schnopp C, Jansson AF, Ayvaz D, Shabashova N, Chernyshova L, Bondarenko A, Moshous D, Neven B, Boubidi C, Ailal F, Giardino G, Del Giacco S, Bougnoux ME, Imai K, Okawa T, Mizoguchi Y, Ozaki Y, Takeuchi M, Hayakawa A, Lögering B, Reich K, Buhl T, Eyerich K, Schaller M, Arkwright PD, Gennery AR, Cant AJ, Warris A, Henriet S, Mekki N, Barbouche R, Ben Mustapha I, Bodemer, Polak M, Grimprel E, Burgel PR, Fischer A, Hermine O, Debré M, Kocacyk D, Dhalla F, Patel SY, Moens L, Haerynck F, Dullaers, Hoste L, Sanal O, Kilic SS, Roesler J, Lanternier F, Lortholary O, Fieschi C, Church JA, Roifman C, Yuenyongviwat A, Peterson P, Boisson-Dupuis S, Abel L, Marciano BE, Netea MG., Toubiana, J., Okada, S., Hiller, J., Oleastro, M., Lagos Gomez, M., Aldave Becerra, J. C., Ouachee-Chardin, M., Fouyssac, F., Girisha, K. M., Etzioni, A., Van Montfrans, J., Camcioglu, Y., Kerns, L. A., Belohradsky, B., Blanche, S., Bousfiha, A., Rodriguez-Gallego, C., Meyts, I., Kisand, K., Reichenbach, J., Renner, E. D., Rosenzweig, S., Grimbacher, B., van de Veerdonk, F. L., Traidl-Hoffmann, C., Picard, C., Marodi, L., Morio, T., Kobayashi, M., Lilic, D., Milner, J. D., Holland, S., Casanova, J. -L., Puel, A, Cypowyj, S, Thumerelle, C, Toulon, A, Bustamante, J, Tahuil, N, Salhi, Dalila, Boiu, S, Chopra, C, Di Giovanni, D, Bezrodnik, L, Boutros, J, Thomas, C, Lacuesta, G, Jannier, S, Korganow, A, Paillard, C, Boutboul, Bué, M, Marie-Cardine, A, Bayart, S, Migaud, M, Weiss, Karmochkine, M, Garcia-Martinez, Jm, Stephan, Jl, Bensaid, P, Jeannoel, Gp, Witte, T, Baumann, U, Harrer, T, Navarrete, C, ACOSTA HUGHES, Benjamin, Firinu, Pignata, C, Picco, P, Mendoza, D, Lugo Reyes, So, Torres Lozano, C, Ortega-Cisneros, M, Cortina, M, Mesdaghi, M, Nabavi, M, Español, T, Martínez-Saavedra, Mt, Rezaei, N, Zoghi, S, Pac, M, Barlogis, V, Revon-Rivière, G, Haimi-Cohen, Y, Spiegel, R, Miron, D, Bouchaib, J, Blancas-Galicia, L, Toth, B, Drexel, B, Rohrlich, P, Lesens, O, Hoernes, M, Drewe, E, Abinum, M, Sawalle-Belohradsky, J, Kindle, G, Depner, M, Milani, L, Nikopensius, T, Remm, M, Talas, Ug, Tucker, M, Willis, M, Leonard, S, Meuwissen, H, Ferdman, Rm, CORBO UGULINO, Wallace, Desai, Mm, Taur, P, Badolato, R, Soltesz, B, Schnopp, C, Jansson, Af, Ayvaz, D, Shabashova, N, Chernyshova, L, Bondarenko, A, Moshous, D, Neven, B, Boubidi, C, Ailal, F, Giardino, G, Del Giacco, S, Bougnoux, Me, Imai, K, Okawa, T, Mizoguchi, Y, Ozaki, Y, Takeuchi, M, Hayakawa, A, Lögering, B, Reich, K, Buhl, T, Eyerich, K, Schaller, M, Arkwright, Pd, Gennery, Ar, Cant, Aj, Warris, A, Henriet, S, Mekki, N, Barbouche, R, Ben Mustapha, I, Bodemer, Polak, M, Grimprel, E, Burgel, Pr, Fischer, A, Hermine, O, Debré, M, Kocacyk, D, Dhalla, F, Patel, Sy, Moens, L, Haerynck, F, Dullaers, Hoste, L, Sanal, O, Kilic, S, Roesler, J, Lanternier, F, Lortholary, O, Fieschi, C, Church, Ja, Roifman, C, Yuenyongviwat, A, Peterson, P, Boisson-Dupuis, S, Abel, L, Marciano, Be, and Netea, Mg.
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Male ,0301 basic medicine ,Pediatrics ,Clinical Trials and Observations ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,medicine.disease_cause ,Biochemistry ,Gastroenterology ,Cohort Studies ,STAT5 Transcription Factor ,Medicine ,Chronic mucocutaneous candidiasis ,Child ,Hematology ,biology ,Progressive multifocal leukoencephalopathy ,Candidiasis, Chronic Mucocutaneous ,Candidiasis ,Orvostudományok ,Middle Aged ,Phenotype ,STAT1 Transcription Factor ,Staphylococcus aureus ,Child, Preschool ,Female ,STAT3 Transcription Factor ,Adult ,Heterozygote ,medicine.medical_specialty ,Adolescent ,Aged ,Genetic Predisposition to Disease ,Humans ,Infant ,Young Adult ,Genetic Association Studies ,Mutation ,Immunology ,Cell Biology ,Chronic Mucocutaneous ,Klinikai orvostudományok ,Herpesviridae ,Mycobacterium tuberculosis ,03 medical and health sciences ,Internal medicine ,Journal Article ,ddc:610 ,Preschool ,Key Points AD STAT1 GOF is the most common genetic cause of inherited CMC and is not restricted to a specific age or ethnic group. STAT1 GOF underlies a variety of infectious and autoimmune features, as well as carcinomas and aneurysms associated with a poor outcome ,Type 1 diabetes ,Cytopenia ,business.industry ,medicine.disease ,biology.organism_classification ,030104 developmental biology ,business - Abstract
Contains fulltext : 172671.pdf (Publisher’s version ) (Closed access) Since their discovery in patients with autosomal dominant (AD) chronic mucocutaneous candidiasis (CMC) in 2011, heterozygous STAT1 gain-of-function (GOF) mutations have increasingly been identified worldwide. The clinical spectrum associated with them needed to be delineated. We enrolled 274 patients from 167 kindreds originating from 40 countries from 5 continents. Demographic data, clinical features, immunological parameters, treatment, and outcome were recorded. The median age of the 274 patients was 22 years (range, 1-71 years); 98% of them had CMC, with a median age at onset of 1 year (range, 0-24 years). Patients often displayed bacterial (74%) infections, mostly because of Staphylococcus aureus (36%), including the respiratory tract and the skin in 47% and 28% of patients, respectively, and viral (38%) infections, mostly because of Herpesviridae (83%) and affecting the skin in 32% of patients. Invasive fungal infections (10%), mostly caused by Candida spp. (29%), and mycobacterial disease (6%) caused by Mycobacterium tuberculosis, environmental mycobacteria, or Bacille Calmette-Guerin vaccines were less common. Many patients had autoimmune manifestations (37%), including hypothyroidism (22%), type 1 diabetes (4%), blood cytopenia (4%), and systemic lupus erythematosus (2%). Invasive infections (25%), cerebral aneurysms (6%), and cancers (6%) were the strongest predictors of poor outcome. CMC persisted in 39% of the 202 patients receiving prolonged antifungal treatment. Circulating interleukin-17A-producing T-cell count was low for most (82%) but not all of the patients tested. STAT1 GOF mutations underlie AD CMC, as well as an unexpectedly wide range of other clinical features, including not only a variety of infectious and autoimmune diseases, but also cerebral aneurysms and carcinomas that confer a poor prognosis.
- Published
- 2016
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