Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
권호 표지
DOI QR코드

DOI QR Code

Chronic Granulomatous Disease on Jeju Island, Korea

  • Cho, Moonjae (Department of Biochemistry, Jeju National University School of Medicine) ;
  • Shin, Kyung-Sue (Division of Clinical Immunology, Department of Pediatrics, Jeju National University School of Medicine)
  • Received : 2013.05.11
  • Accepted : 2013.06.15
  • Published : 2013.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Chronic granulomatous disease (CGD) is a rare inherited disorder of a defective NADPH oxidase enzyme, resulting in very low or no production of superoxide and subsequent reactive oxygen species. Consequently, patients with CGD are highly susceptible to severe bacterial and fungal infections. CGD is a genetically heterogeneous disease caused by defects in any one of the genes encoding the NADPH oxidase components. CGD generally affects about 3-4 per 1,000,000 individuals; thus, it is surprising that the prevalence of CGD on Jeju Island is 34.3 per 1,000,000 individuals. At present, 20 patients with CGD from 14 unrelated families on Jeju Island have been identified; nine males and 11 females. All patients with CGD tested on Jeju Island had an identical and homozygous mutation (c.7C>T in CYBA, p.Q3X in $p22^{phox}$). Therefore, all patients were autosomal recessive form of CGD. This strongly suggests that the unique and identical mutation in CYBA may be inherited from a common proband. Using mutation-specific primers to detect the mutated allele in CYBA, the frequency of subjects carrying a mutated allele was 1.3% of enrolled subjects from Seogwipo City. Further studies are necessary to elucidate how frequently this mutant allele occurs in the population on Jeju Island. Additionally, it is important to construct a national registry system to understand the pathophysiology of CGD and develop a strategy for long-term therapy.

Keywords

References

  1. Segal BH, Veys P, Malech H, Cowan MJ. Chronic granulomatous disease: lessons from a rare disorder. Biol Blood Marrow Transplant 2011;17:S123-31. https://doi.org/10.1016/j.bbmt.2010.09.008
  2. Heyworth PG, Cross AR, Curnutte JT. Chronic granulomatous disease. Curr Opin Immunol 2003;15:578-84. https://doi.org/10.1016/S0952-7915(03)00109-2
  3. Winkelstein JA, Marino MC, Johnston RB Jr, Boyle J, Curnutte J, Gallin JI, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore) 2000;79:155-69. https://doi.org/10.1097/00005792-200005000-00003
  4. van den Berg JM, van Koppen E, Ahlin A, Belohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PLoS One 2009;4:e5234. https://doi.org/10.1371/journal.pone.0005234
  5. Kang EM, Marciano BE, DeRavin S, Zarember KA, Holland SM, Malech HL. Chronic granulomatous disease: overview and hematopoietic stem cell transplantation. J Allergy Clin Immunol 2011;127:1319-26. https://doi.org/10.1016/j.jaci.2011.03.028
  6. Kuijpers T, Lutter R. Inflammation and repeated infections in CGD: two sides of a coin. Cell Mol Life Sci 2012;69:7-15. https://doi.org/10.1007/s00018-011-0834-z
  7. Stasia MJ, Li XJ. Genetics and immunopathology of chronic granulomatous disease. Semin Immunopathol 2008;30:209-35. https://doi.org/10.1007/s00281-008-0121-8
  8. Roos D, Kuhns DB, Maddalena A, Roesler J, Lopez JA, Ariga T, et al. Hematologically important mutations: X-linked chronic granulomatous disease (third update). Blood Cells Mol Dis 2010;45:246-65. https://doi.org/10.1016/j.bcmd.2010.07.012
  9. Roos D, Kuhns DB, Maddalena A, Bustamante J, Kannengiesser C, de Boer M, et al. Hematologically important mutations: the autosomal recessive forms of chronic granulomatous disease (second update). Blood Cells Mol Dis 2010;44:291-9. https://doi.org/10.1016/j.bcmd.2010.01.009
  10. Matute JD, Arias AA, Wright NA, Wrobel I, Waterhouse CC, Li XJ, et al. A new genetic subgroup of chronic granulomatous disease with autosomal recessive mutations in p40 phox and selective defects in neutrophil NADPH oxidase activity. Blood 2009;114:3309-15. https://doi.org/10.1182/blood-2009-07-231498
  11. Rhim JW, Kim KH, Kim DS, Kim BS, Kim JS, Kim CH, et al. Prevalence of primary immunodeficiency in Korea. J Korean Med Sci 2012;27:788-93. https://doi.org/10.3346/jkms.2012.27.7.788
  12. Kim JG, Shin KS, Park JS. Clinical Study on Chronic Granulomatous Disease in Korea. Korean J Immunol 1999;21:271-83.
  13. Kim YM, Park JE, Kim JY, Lim HK, Nam JK, Cho M, et al. Genetic analysis of 10 unrelated Korean families with p22-phox-deficient chronic granulomatous disease: an unusually identical mutation of the CYBA gene on Jeju Island, Korea. J Korean Med Sci 2009;24:1045-50. https://doi.org/10.3346/jkms.2009.24.6.1045
  14. Jirapongsananuruk O, Malech ML, Kuhns DB, Niemela JE, Brown MR, Anderson-Cohen M, et al. Diagnostic paradigm for evaluation of male patients with chronic granulomatous disease, based on the dihydrorhodamine 123 assay. J Allergy Clin Immunol 2003;111:374-9. https://doi.org/10.1067/mai.2003.58
  15. Crockard AD, Thompson JM, Boyd NA, Haughton DJ, McCluskey DR, Turner CP. Diagnosis and carrier detection of chronic granulomatous disease in five families by flow cytometry. Int Arch Allergy Immunol 1997;114:144-52. https://doi.org/10.1159/000237660
  16. Parkos CA, Dinauer MC, Jesaitis AJ, Orkin SH, Curnutte JT. Absence of both the 91kD and 22kD subunits of human neutrophil cytochrome b in two genetic forms of chronic granulomatous disease. Blood 1989; 73:1416-20.
  17. Rae J, Noack D, Heyworth PG, Ellis BA, Curnutte JT, Cross AR. Molecular analysis of 9 new families with chronic granulomatous disease caused by mutations in CYBA , the gene encoding p22(phox ). Blood 2000;96: 1106-12.
  18. Yamada M, Ariga T, Kawamura N, Ohtsu M, Imajoh-Ohmi S, Ohshika E, et al. Genetic studies of three Japanese patients with p22-phox-deficient chronic granulomatous disease: detection of a possible common mutant CYBA allele in Japan and a genotype-phenotype correlation in these patients. Br J Haematol 2000;108:511-7. https://doi.org/10.1046/j.1365-2141.2000.01857.x
  19. Yu L, Zhen L, Dinauer MC. Biosynthesis of the phagocyte NADPH oxidase cytochrome b558. Role of heme incorporation and heterodimer formation in maturation and stability of gp91phox and p22phox subunits. J Biol Chem 1997;272:27288-94. https://doi.org/10.1074/jbc.272.43.27288
  20. DeLeo FR, Burritt JB, Yu L, Jesaitis AJ, Dinauer MC, Nauseef WM. Processing and maturation of flavocytochrome b558 include incorporation of heme as a prerequisite for heterodimer assembly. J Biol Chem 2000; 275:13986-93. https://doi.org/10.1074/jbc.275.18.13986
  21. Kim YM, Shin KS, Cho M. New method for detection of p22-phox - deficient chronic granulomatous disease heterozygote carriers in Jeju. J Korean Soc Appl Biol Chem 2012;55:595-8. https://doi.org/10.1007/s13765-012-2134-1
  22. Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007;87:245-313. https://doi.org/10.1152/physrev.00044.2005
  23. Kleniewska P, Piechota A, Skibska B, Gorąca A. The NADPH oxidase family and its inhibitors. Arch Immunol Ther Exp (Warsz) 2012;60:277-94. https://doi.org/10.1007/s00005-012-0176-z
  24. Wolach B, Gavrieli R, de Boer M, Gottesman G, Ben-Ari J, Rottem M, et al. Chronic granulomatous disease in Israel: clinical, functional and molecular studies of 38 patients. Clin Immunol 2008;129:103-14. https://doi.org/10.1016/j.clim.2008.06.012
  25. Teimourian S, Zomorodian E, Badalzadeh M, Pouya A, Kannengiesser C, Mansouri D, et al. Characterization of six novel mutations in CYBA: the gene causing autosomal recessive chronic granulomatous disease. Br J Haematol 2008;141:848-51. https://doi.org/10.1111/j.1365-2141.2008.07148.x
  26. Dinauer MC, Pierce EA, Erickson RW, Muhlebach TJ, Messner H, Orkin SH, et al. Point mutation in the cytoplasmic domain of the neutrophil p22-phox cytochrome b subunit is associated with a nonfunctional NADPH oxidase and chronic granulomatous disease. Proc Natl Acad Sci U S A 1991;88:11231-5. https://doi.org/10.1073/pnas.88.24.11231
  27. Nunoi H. Two breakthroughs in CGD studies. Nihon Rinsho Meneki Gakkai Kaishi 2007;30:1-10. https://doi.org/10.2177/jsci.30.1
  28. Oh HB, Park JS, Lee W, Yoo SJ, Yang JH, Oh SY. Molecular analysis of X-linked chronic granulomatous disease in five unrelated Korean patients. J Korean Med Sci 2004;19:218-22. https://doi.org/10.3346/jkms.2004.19.2.218
  29. Lee SY, Choi EY, Go SH, Rhim JW, Lee SD, Kim JG. A Case of X-linked Chronic Granulomatous Disease Diagnosed in Identical Twin. Infect Chemother 2007;39:332-7.