An Iranian Patient Suffering from Chronic Granulomatous Disease, with Mutation in the NCF1 Gene
Abstract
Chronic granulomatous disease (CGD) is an innate immunodeficiency characterized by an increased susceptibility to recurrent infections and granulomatous inflammation. CGD results from the loss of phagocyte superoxide production caused by a failure of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme. It is caused by recessive mutations in any of four genes that encode subunits of the NADPH oxidase. The most common autosomal recessive form of CGD is p47phox encoded by the NCF1 gene which is clinically milder. In this case study, we report a boy with lung abscess and recurrent oral thrush presentations. Whole exome sequencing (WES) test was performed to identify the underlying genetic mutation in this patient. WES of the patient reported a homozygous deletion mutation in the NCF1 gene (NM_608512: exon2: c.75_76delGT). Our data shows that early detection of NCF1 mutation has a wide heterogeneity in clinical manifestations of the patients.
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3. Van den Berg JM, van Koppen E, Ahlin A, Be-lohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PloS one. 2009;4(4):e5234.
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12. Agudelo-Florez P, Prando-Andrade CC, Lopez JA, Costa-Carvalho BT, Quezada A, Espinosa FJ, et al. Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics. Pediatr blood cancer. 2006;46(2):243-52.
13. Koker MY, Camcioglu Y, van Leeuwen K, Kilic SS, Barlan I, Yilmaz M, et al. Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients. J Allergy Clin Immunol. 2013;132(5):1156-63.e5.
14. Wolach B, Gavrieli R, de Boer M, van Leeuwen K, Wolach O, Grisaru-Soen G, et al. Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A). J clin immunol. 2018;38(2):193-203.
15. Kulkarni M, Desai M, Gupta M, Dalvi A, Taur P, Terrance A, et al. Clinical, Immunological, and Molecular Findings of Patients with p47(phox) Defect Chronic Granulomatous Disease (CGD) in Indian Families. J clin immunol. 2016;36(8):774-84.
16. El-Benna J, Dang P, Gougerot-Pocidalo M, Marie J-C, Braut-Boucher F. p47phox, the phagocyte NADPH oxidase/NOX2 organizer: Structure, phosphorylation and implication in diseases. Exp Mol Med. 2009;41:217-25.
17. Roesler J, Curnutte JT, Rae J, Barrett D, Patino P, Chanock SJ, et al. Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease. Blood. 2000;95(6):2150-6.
18. Movahedi M, Aghamohammadi A, Rezaei N, Farhoudi A, Pourpak Z, Moin M, et al. Gastrointestinal manifestations of patients with chronic granulomatous disease. Iran J Allergy Asthma Immunol. 2004;3(2):83-7.
19. Barton LL, Moussa SL, Villar RG, Hulett RL. Gastrointestinal complications of chronic granulomatous disease: case report and literature review. Clin Pediatr (Phila). 1998;37(s4):231- 6.
20. Lublin M, Bartlett DL, Danforth DN, Kauffman H, Gallin JI, Malech HL, et al. Hepatic abscess in patients with chronic granulomatous disease. Ann Surg. 2002;235(3):383-91.
21. Blancas-Galicia L, Santos-Chávez E, Deswarte C, Mignac Q, Medina-Vera I, LeónLara X, et al. Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease. J clin immunol. 2020:10.1007/s10875- 020-00750-5.
22.Hanoglu D, Ozgür TT, Ayvaz D, Köker MY, Sanal O. Chronic granulomatous disease presenting with hypogammaglobulinemia. J Investig Allergol Clin Immunol. 2011;21(4):310-2.
23. Patiroglu T, Gungor HE, Lazaroski S, Unal E. Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome. Acta Microbiol Immunol Hung. 2013;60(2):155-62.
24. Bazregari S, Azizi G, Tavakol M, Asgardoon MH, Kiaee F, Tavakolinia N, et al. Evaluation of infectious and non-infectious complications in patients with primary immunodeficiency. Cent Eur J Immunol. 2017;42(4):336-41.
25. Keleş S, Soysal A, Özdemir C, Eifan AO, Bahçeciler N, Bakır M, et al. Chronic granulomatous disease presenting with invasive aspergillosis and hypogammaglobulinemia. Asthma Allergy Immunol. 2016;7(3):189-93.
2. 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. 2000;79(3):155-69.
3. Van den Berg JM, van Koppen E, Ahlin A, Be-lohradsky BH, Bernatowska E, Corbeel L, et al. Chronic granulomatous disease: the European experience. PloS one. 2009;4(4):e5234.
4. Wolach B, Gavrieli R, de Boer M, van Leeuwen K, Berger-Achituv S, Stauber T, et al. Chronic granulomatous disease: Clinical, functional, molecular, and genetic studies. The Israeli experience with 84 patients. Am J Hematol. 2017;92(1):28-36.
5. Holland SM. Chronic Granulomatous Disease. Hematology/Oncology Clinics. 2013;27(1):89-99.
6. Stasia MJ, Li XJ, editors. Genetics and immunopathology of chronic granulomatous disease. Seminars in immunopathology; 2008: Springer.
7. Kruger P, Saffarzadeh M, Weber ANR, Rieber N, Radsak M, von Bernuth H, et al. Neutrophils:Between Host Defence, Immune Modulation, and Tissue Injury. PLOS Pathogens. 2015;11(3):e1004651.
8. Diebold BA, Bokoch GM. Molecular basis for Rac2 regulation of phagocyte NADPH oxidase. Nat Immunol. 2001;2(3):211-5.
9. Knaus UG, Heyworth PG, Evans T, Curnutte JT, Bokoch GM. Regulation of phagocyte oxygen radical production by the GTP-binding protein Rac 2. Science. 1991;254(5037):1512-5 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(15):3309-15.
11. Al-Zadjali S, Al-Tamemi S, Elnour I, AlKindi S, Lapoumeroulie C, Al-Maamari S, et al. Clinical and molecular findings of chronic granulomatous disease in Oman: family studies. Clin Genet. 2015;87(2):185-9.
12. Agudelo-Florez P, Prando-Andrade CC, Lopez JA, Costa-Carvalho BT, Quezada A, Espinosa FJ, et al. Chronic granulomatous disease in Latin American patients: clinical spectrum and molecular genetics. Pediatr blood cancer. 2006;46(2):243-52.
13. Koker MY, Camcioglu Y, van Leeuwen K, Kilic SS, Barlan I, Yilmaz M, et al. Clinical, functional, and genetic characterization of chronic granulomatous disease in 89 Turkish patients. J Allergy Clin Immunol. 2013;132(5):1156-63.e5.
14. Wolach B, Gavrieli R, de Boer M, van Leeuwen K, Wolach O, Grisaru-Soen G, et al. Analysis of Chronic Granulomatous Disease in the Kavkazi Population in Israel Reveals Phenotypic Heterogeneity in Patients with the Same NCF1 mutation (c.579G>A). J clin immunol. 2018;38(2):193-203.
15. Kulkarni M, Desai M, Gupta M, Dalvi A, Taur P, Terrance A, et al. Clinical, Immunological, and Molecular Findings of Patients with p47(phox) Defect Chronic Granulomatous Disease (CGD) in Indian Families. J clin immunol. 2016;36(8):774-84.
16. El-Benna J, Dang P, Gougerot-Pocidalo M, Marie J-C, Braut-Boucher F. p47phox, the phagocyte NADPH oxidase/NOX2 organizer: Structure, phosphorylation and implication in diseases. Exp Mol Med. 2009;41:217-25.
17. Roesler J, Curnutte JT, Rae J, Barrett D, Patino P, Chanock SJ, et al. Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease. Blood. 2000;95(6):2150-6.
18. Movahedi M, Aghamohammadi A, Rezaei N, Farhoudi A, Pourpak Z, Moin M, et al. Gastrointestinal manifestations of patients with chronic granulomatous disease. Iran J Allergy Asthma Immunol. 2004;3(2):83-7.
19. Barton LL, Moussa SL, Villar RG, Hulett RL. Gastrointestinal complications of chronic granulomatous disease: case report and literature review. Clin Pediatr (Phila). 1998;37(s4):231- 6.
20. Lublin M, Bartlett DL, Danforth DN, Kauffman H, Gallin JI, Malech HL, et al. Hepatic abscess in patients with chronic granulomatous disease. Ann Surg. 2002;235(3):383-91.
21. Blancas-Galicia L, Santos-Chávez E, Deswarte C, Mignac Q, Medina-Vera I, LeónLara X, et al. Genetic, Immunological, and Clinical Features of the First Mexican Cohort of Patients with Chronic Granulomatous Disease. J clin immunol. 2020:10.1007/s10875- 020-00750-5.
22.Hanoglu D, Ozgür TT, Ayvaz D, Köker MY, Sanal O. Chronic granulomatous disease presenting with hypogammaglobulinemia. J Investig Allergol Clin Immunol. 2011;21(4):310-2.
23. Patiroglu T, Gungor HE, Lazaroski S, Unal E. Chronic granulomatous disease with markedly elevated IgE levels mimicking hyperimmunoglobulin E syndrome. Acta Microbiol Immunol Hung. 2013;60(2):155-62.
24. Bazregari S, Azizi G, Tavakol M, Asgardoon MH, Kiaee F, Tavakolinia N, et al. Evaluation of infectious and non-infectious complications in patients with primary immunodeficiency. Cent Eur J Immunol. 2017;42(4):336-41.
25. Keleş S, Soysal A, Özdemir C, Eifan AO, Bahçeciler N, Bakır M, et al. Chronic granulomatous disease presenting with invasive aspergillosis and hypogammaglobulinemia. Asthma Allergy Immunol. 2016;7(3):189-93.
| Files | ||
| Issue | Vol 3, No 1 (2020) | |
| Section | Case Report | |
| DOI | https://doi.org/10.22034/igj.2020.225558.1037 | |
| Keywords | ||
| Chronic granulomatous disease (CGD) NCF1 gene nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme p47Phox | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Salami F, Mozafari Nezhad R, Shariati S, Mirminachi B. An Iranian Patient Suffering from Chronic Granulomatous Disease, with Mutation in the NCF1 Gene. Immunol Genet J. 2020;3(1):64-70.
