Chronic mucocutaneous Candidiasis caused by a novel STAT1 mutation: a report of 4 patients
Abstract
Background: Chronic mucocutaneous Candidiasis (CMCC) is characterized by recurrent or persistent fungal infections of the skin, nails, and oral and genital mucosae. There are several underlying genetic causes for CMCC, with mutations in Signal Transducer and Activator of Transcription-1 (STAT1) accounting for the majority of cases.
Aim: To broaden the genotypic spectrum of CMCC caused by STAT1 mutations.
Methods: We evaluated a young patient and her family with CMCC. Immune workup and targeted gene sequencing were performed.
Results: The proband presented at 7 years of age with persistent oral thrush. Immune evaluation revealed her cellular and humoral immunity to be within normal range. Given that her family history was significant for oral lesions in father, siblings, and paternal family members, STAT1 gene sequencing was performed. A novel heterozygous missense c.G799A, predicting a p. Ala267Thr amino acid change within the coiled-coil domain, was identified in our patient and 3 of her family members.
Conclusion: Gain-of-function mutations in STAT1 have been associated with a variety of phenotypes, ranging from isolated CMCC to severe fatal combined immunodeficiency, mycobacterial infections, autoimmune disorders, as well as malignancy and aneurysms. Here, we describe a novel STAT1 mutation, c.G799A, resulting in a very mild phenotype of isolated CMCC in 4 members of one kindred.
Statement of novelty: We describe 4 patients with a mild phenotype of CMCC caused by a novel STAT1 heterozygous mutation.
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REFERENCES
Breuer O., Daum H., Cohen-Cymberknoh M., Unger S., Shoseyov D., Stepensky P., Keller B., Warnatz K., and Kerem E. 2017. Autosomal dominant gain of function STAT1 mutation and severe bronchiectasis. Respir. Med. 126: 39–45.
Gough D.J., Levy D.E., Johnstone R.W., and Clarke C.J. 2008. IFNγ signaling—Does it mean JAK-STAT? Cytokine Growth Factor Rev. 19: 383–394.
Koo S., Kejariwal D., Al-Shehri T., Dhar A., and Lilic D. 2017. Oesophageal candidiasis and squamous cell cancer in patients with gain-of-function STAT1 gene mutation. United Eur. Gastroenterol. J. 5: 625–631.
Levy D.E. and Darnell J.E. Jr. 2002. STATs: Transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 3: 651–662.
Liu L., Okada S., Kong X.F., Kreins A.Y., Cypowyj S., Abhyankar A., Toubiana J., Itan Y., Audry M., Nitschke P., Masson C., Toth B., Flatot J., Migaud M., Chrabieh M., Kochetkov T., Bolze A., Borghesi A., Toulon A., Hiller J., Eyerich S., Eyerich K., Gulácsy V., Chernyshova L., Chernyshov V., Bondarenko A., Grimaldo R.M., Blancas-Galicia L., Beas I.M., Roesler J., Magdorf K., Engelhard D., Thumerelle C., Burgel P.R., Hoernes M., Drexel B., Seger R., Kusuma T., Jansson A.F., Sawalle-Belohradsky J., Belohradsky B., Jouanguy E., Bustamante J., Bué M., Karin N., Wildbaum G., Bodemer C., Lortholary O., Fischer A., Blanche S., Al-Muhsen S., Reichenbach J., Kobayashi M., Rosales F.E., Lozano C.T., Kilic S.S., Oleastro M., Etzioni A., Traidl-Hoffmann C., Renner E.D., Abel L., Picard C., Maródi L., Boisson-Dupuis S., Puel A., and Casanova J.L. 2011. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J. Exp. Med. 208: 1635–1648.
Sampaio E.P., Hsu A.P., Pechacek J., Bax H.I., Dias D.L., Paulson M.L., Chandrasekaran P., Rosen L.B., Carvalho D.S., Ding L., Vinh D.C., Browne S.K., Datta S., Milner J.D., Kuhns D.B., Long Priel D.A., Sadat M.A., Shiloh M., De Marco B., Alvares M., Gillman J.W., Ramarathnam V., de la Morena M., Bezrodnik L., Moreira I., Uzel G., Johnson D., Spalding C., Zerbe C.S., Wiley H., Greenberg D.E., Hoover S.E., Rosenzweig S.D., Galgiani J.N., and Holland S.M. 2013. Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis. J. Allergy Clin. Immunol. 131(6): 1624–1634.e17.
Sharfe N., Nahum A., Newell A., Dadi H., Ngan B., Pereira S.L., Herbrick J.A., and Roifman C.M. 2014. Fatal combined immunodeficiency associated with heterozygous mutation in STAT1. J. Allergy Clin. Immunol. 133: 807–817.
Tangye S.G., Al-Herz W., Bousfiha A., Chatila T., Cunningham-Rundles C., Etzioni A., Franco J.L., Holland S.M., Klein C., Morio T., Ochs H.D., Oksenhendler E., Picard C., Puck J., Torgerson T.R., Casanova J.L., and Sullivan K.E. 2020. Human inborn errors of immunity: 2019 update on the classification from the International Union of Immunological Societies Expert Committee. J. Clin. Immunol. 40: 24–64.
Toubiana J., Okada S., Hiller J., Oleastro M., Lagos Gomez M., Aldave Becerra J.C., Ouachée-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., and Puel A., and International STAT1 Gain-of-Function Study Group. 2016. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood, 127: 3154–3164.
van de Veerdonk F.L., Plantinga T.S., Hoischen A., Smeekens S.P., Joosten L.A., Gilissen C., Arts P., Rosentul D.C., Carmichael A.J., Smits-van der Graaf C.A., Kullberg B.J., van der Meer J.W., Lilic D., Veltman J.A., and Netea M.G. 2011. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N. Engl. J. Med. 365: 54–61.
Zheng J., van de Veerdonk F.L., Crossland K.L., Smeekens S.P., Chan C.M., Al Shehri T., Abinun M., Gennery A.R., Mann J., Lendrem D.W., Netea M.G., Rowan A.D., and Lilic D. 2015. Gain-of-function STAT1 mutations impair STAT3 activity in patients with chronic mucocutaneous candidiasis (CMC). Eur. J. Immunol. 45: 2834–2846.
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Published In
LymphoSign Journal
Volume 8 • Number 2 • June 2021
Pages: 64 - 67
History
Received: 8 May 2021
Accepted: 20 May 2021
Accepted manuscript online: 2 June 2021
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© 2021.
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JennyGarkaby and OriScott. 2021. Chronic mucocutaneous Candidiasis caused by a novel STAT1 mutation: a report of 4 patients. LymphoSign Journal.
8(2): 64-67. https://doi.org/10.14785/lymphosign-2021-0019
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