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

dc.creatorFranco Restrepo, José Luis
dc.creatorOrrego Arango, Julio César
dc.creatorDepner, Mark
dc.creatorFuchs, Sebastian
dc.creatorRaabe, Jan
dc.creatorFrede, Natalie
dc.creatorGlocker, Cristina
dc.creatorDoffinger, Rainer
dc.creatorGkrania Klotsas, Effrossyni
dc.creatorKumararatne, Dinakantha
dc.creatorAtkinson, T Prescott
dc.creatorSchroeder Jr, Harry W.
dc.creatorNiehues, Tim
dc.creatorDückers, Gregor
dc.creatorStray Pedersen, Asbjørg
dc.creatorBaumann, Ulrich
dc.creatorSchmidt, Reinhold
dc.creatorBen Shoshan, Moshe
dc.creatorMcCusker, Christine
dc.creatorAbe Jacob, Cristina Miuki
dc.creatorCarneiro Sampaio, Magda
dc.creatorDevlin, Lisa A.
dc.creatorM Edgar, J David
dc.creatorHenderson, Paul
dc.creatorRussell, Richard K
dc.creatorSkytte, Anne Bine
dc.creatorSeneviratne, Suranjith L.
dc.creatorWanders, Jennifer
dc.creatorStauss, Hans
dc.creatorMeyts, Isabelle
dc.creatorMoens, Leen
dc.creatorJesenak, Milos
dc.creatorKobbe, Robin
dc.creatorBorte, Stephan
dc.creatorBorte, Michael
dc.creatorWright, Dowain A
dc.creatorHagin, David
dc.creatorTorgerson, Troy R
dc.creatorGrimbacher, Bodo
dc.date2023-02-03T22:02:13Z
dc.date2023-02-03T22:02:13Z
dc.date2016
dc.date.accessioned2024-04-23T17:57:31Z
dc.date.available2024-04-23T17:57:31Z
dc.identifierDepner M, Fuchs S, Raabe J, Frede N, Glocker C, Doffinger R, Gkrania-Klotsas E, Kumararatne D, Atkinson TP, Schroeder HW Jr, Niehues T, Dückers G, Stray-Pedersen A, Baumann U, Schmidt R, Franco JL, Orrego J, Ben-Shoshan M, McCusker C, Jacob CM, Carneiro-Sampaio M, Devlin LA, Edgar JD, Henderson P, Russell RK, Skytte AB, Seneviratne SL, Wanders J, Stauss H, Meyts I, Moens L, Jesenak M, Kobbe R, Borte S, Borte M, Wright DA, Hagin D, Torgerson TR, Grimbacher B. The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1. J Clin Immunol. 2016 Jan;36(1):73-84. doi: 10.1007/s10875-015-0214-9.
dc.identifier0271-9142
dc.identifierhttps://hdl.handle.net/10495/33357
dc.identifier10.1007/s10875-015-0214-9
dc.identifier1573-2592
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9230162
dc.descriptionABSTRACT: 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.
dc.descriptionCOL0012426
dc.format12
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherSpringer
dc.publisherInmunodeficiencias Primarias
dc.publisherNueva York, Estados Unidos
dc.relationJ. Clin. Immunol.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectCandidiasis Mucocutánea Crónica
dc.subjectCandidiasis, Chronic Mucocutaneous
dc.subjectCélulas Cultivadas
dc.subjectCells, Cultured
dc.subjectFosforilación
dc.subjectPhosphorylation
dc.subjectFactor de Transcripción STAT1
dc.subjectSTAT1 Transcription Factor
dc.subjectSíndromes de Inmunodeficiencia
dc.subjectImmunologic Deficiency Syndromes
dc.subjectLeucocitos Mononucleares
dc.subjectLeukocytes, Mononuclear
dc.subjectEstructura Terciaria de Proteína
dc.subjectProtein Structure, Tertiary
dc.titleThe Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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