Journal of Genetic Medicine

  • 제15권2호
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  • Pages.92-96
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  • 2018
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  • 1226-1769(pISSN)
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  • 2383-8442(eISSN)
대한의학유전학회 (Korean Society of Medical Genetics and Genomics)
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First Korean case of a STAT1 gene mutation: chronic mucocutaneous candidiasis, hypothyroidism, chronic hepatitis and systemic lupus erythematosus

  • Kim, Kang-in (Department of Pediatrics, Soonchunhyang University Seoul Hospital) ;
  • Lee, Hanbyul (Department of Pediatrics, Soonchunhyang University Seoul Hospital) ;
  • Jung, So Yoon (Department of Pediatrics, Soonchunhyang University Seoul Hospital) ;
  • Lee, Dong Hwan (Department of Pediatrics, Soonchunhyang University Seoul Hospital) ;
  • Lee, Jeongho (Department of Pediatrics, Soonchunhyang University Seoul Hospital)
  • 투고 : 2018.05.16
  • 심사 : 2018.07.25
  • 발행 : 2018.12.31
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초록

Chronic mucocutaneous candidiasis (CMC) is characterized by increased susceptibility to chronic and recurrent infections of the skin, mucous membranes, and nails by Candida species. It is a primary immunodeficiency disorder that is difficult to diagnose because of its heterogeneous clinical manifestations and genetic background. A 20-month-old boy who did not grow in height for 3 months was diagnosed as having hypothyroidism and he had hepatitis which was found at 5 years old. He presented with persistent oral thrush and vesicles on the body, the cause of which could not be identified from laboratory findings. No microorganism was detected in the throat culture; however, the oral thrush persisted. Immunological tests showed that immunoglobulin (Ig) subclass IgG and cluster of differentiation (CD)3, CD4, and CD8 levels were within normal limits. We prescribed oral levothyroxine and fluconazole mouth rinse. The patient was examined using diagnostic exome sequencing at the age of 6 years, and a c.1162A>G (p.K388E) STAT1 gene mutation was identified. A diagnosis of CMC based on the STAT1 gene mutation was, thus, made. At the age of 8 years, the boy developed a malar-like rash on his face. We conducted tests for detection of antinuclear antibodies and anti-dsDNA antibodies, which showed positive results; therefore, systemic lupus erythematosus (SLE) was also suspected. Whole exome sequencing is important to diagnose rare diseases in children. A STAT1 gene mutation should be suspected in patients with chronic fungal infections with a thyroid disease and/or SLE.

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참고문헌

  1. van de Veerdonk FL, Plantinga TS, Hoischen A, Smeekens SP, Joosten LA, Gilissen C, et al. STAT1 mutations in autosomal dominant chronic mucocutaneous candidiasis. N Engl J Med 2011;365:54-61. https://doi.org/10.1056/NEJMoa1100102
  2. Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, Aldave Becerra JC, et al. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 2016;127:3154-64. https://doi.org/10.1182/blood-2015-11-679902
  3. Depner M, Fuchs S, Raabe J, Frede N, Glocker C, Doffinger R, et al. The extended clinical phenotype of 26 patients with chronic mucocutaneous candidiasis due to gain-of-function mutations in STAT1. J Clin Immunol 2016;36:73-84. https://doi.org/10.1007/s10875-015-0214-9
  4. Dhalla F, Fox H, Davenport EE, Sadler R, Anzilotti C, van Schouwenburg PA, et al. Chronic mucocutaneous candidiasis: characterization of a family with STAT-1 gain-of-function and development of an exvivo assay for Th17 deficiency of diagnostic utility. Clin Exp Immunol 2016;184:216-27. https://doi.org/10.1111/cei.12746
  5. Soltesz B, Toth B, Shabashova N, Bondarenko A, Okada S, Cypowyj S, et al. New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe. J Med Genet 2013;50:567-78. https://doi.org/10.1136/jmedgenet-2013-101570
  6. Smeekens SP, Plantinga TS, van de Veerdonk FL, Heinhuis B, Hoischen A, Joosten LA, et al. STAT1 hyperphosphorylation and defective IL12R/IL23R signaling underlie defective immunity in autosomal dominant chronic mucocutaneous candidiasis. PLoS One 2011;6:e29248. https://doi.org/10.1371/journal.pone.0029248
  7. Liang Y, Xu WD, Yang XK, Fang XY, Liu YY, Ni J, et al. Association of signaling transducers and activators of transcription 1 and systemic lupus erythematosus. Autoimmunity 2014;47:141-5. https://doi.org/10.3109/08916934.2013.873415
  8. Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med 2011;208:1635-48. https://doi.org/10.1084/jem.20110958
  9. Conti HR, Shen F, Nayyar N, Stocum E, Sun JN, Lindemann MJ, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 2009;206:299-311. https://doi.org/10.1084/jem.20081463
  10. Takezaki S, Yamada M, Kato M, Park MJ, Maruyama K, Yamazaki Y, et al. Chronic mucocutaneous candidiasis caused by a gain-of-function mutation in the STAT1 DNA-binding domain. J Immunol 2012;189:1521-6. https://doi.org/10.4049/jimmunol.1200926
  11. Hori T, Ohnishi H, Teramoto T, Tsubouchi K, Naiki T, Hirose Y, et al. Autosomal-dominant chronic mucocutaneous candidiasis with STAT1-mutation can be complicated with chronic active hepatitis and hypothyroidism. J Clin Immunol 2012;32:1213-20. https://doi.org/10.1007/s10875-012-9744-6
  12. Frans G, Moens L, Schaballie H, Van Eyck L, Borgers H, Wuyts M, et al. Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1): chronic mucocutaneous candidiasis accompanied by enamel defects and delayed dental shedding. J Allergy Clin Immunol 2014;134:1209-13.e6. https://doi.org/10.1016/j.jaci.2014.05.044
  13. Wang X, Zhang R, Wu W, Wang A, Wan Z, van de Veerdonk FL, et al. New and recurrent STAT1 mutations in seven Chinese patients with chronic mucocutaneous candidiasis. Int J Dermatol 2017;56:e30-3. https://doi.org/10.1111/ijd.13427
  14. van de Veerdonk FL, Netea MG. Treatment options for chronic mucocutaneous candidiasis. J Infect 2016;72 Suppl:S56-60. https://doi.org/10.1016/j.jinf.2016.04.023
  15. Wildbaum G, Shahar E, Katz R, Karin N, Etzioni A, Pollack S. Continuous G-CSF therapy for isolated chronic mucocutaneous candidiasis: complete clinical remission with restoration of IL-17 secretion. J Allergy Clin Immunol 2013;132:761-4. https://doi.org/10.1016/j.jaci.2013.04.018
  16. Higgins E, Al Shehri T, McAleer MA, Conlon N, Feighery C, Lilic D, et al. Use of ruxolitinib to successfully treat chronic mucocutaneous candidiasis caused by gain-of-function signal transducer and activator of transcription 1 (STAT1) mutation. J Allergy Clin Immunol 2015;135:551-3. https://doi.org/10.1016/j.jaci.2014.12.1867
  17. Chun TJ, Ro BI. Chronic mucocutaneous candidiasis in Korea. Korean J Med Mycol 1999;4:104-8.
  18. Choi KH, Kim HS, Kim HO, Park YM. Familial chronic mucocutaneous candidiasis. Korean J Med Mycol 2009;14:28-32.
  19. Park JH, Yoo CS, Kil MS, Kim CW, Kim SS, Kim KH. A case of chronic mucocutaneous candidiasis occurring in a patient with scrofuloderma-like BCGitis. Korean J Med Mycol 2010;15:175-81.
  20. Lee HK, Seo SJ, Ro BI. A case of chronic mucocutaneous candidiasis. Ann Dermatol 1995;7:62-5. https://doi.org/10.5021/ad.1995.7.1.62