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Journal of Clinical Immunology

, Volume 37, Issue 2, pp 109–112 | Cite as

Chronic Granulomatous Disease Due to Neutrophil Cytosolic Factor (NCF2) Gene Mutations in Three Unrelated Families

  • Pandiarajan Vignesh
  • Amit Rawat
  • Ankur Kumar
  • Deepti Suri
  • Anju Gupta
  • Yu L Lau
  • Koon W Chan
  • Surjit Singh
Letter to Editor

Abstract

Chronic granulomatous disease (CGD) is an inheritable and genetically heterogeneous disease resulting from mutations in different subcomponents of the NADPH oxidase system. Mutations in the NCF2 gene account for <5% of all cases of CGD. We analyzed the clinical and laboratory findings of CGD with mutations in the NCF2 gene from amongst our cohort of CGD patients. A homozygous mutation (c.835_836delAC, p.T279fsX294), a deletion in NCF2 gene was found in two cases. In the third case, two heterozygous mutations were detected, IVS13-2A>T on one allele and c.1099C>T (p.) on the other allele. The mother of this child was a carrier for the IVS13-2A>T mutation. All three cases had colitis, and it was the initial symptom in two patients. One of the patients also developed a lung abscess due to Nocardia cyriacigeorgica.

Keywords

Chronic granulomatous disease neutrophil cytosolic fraction 2 gene mutation autosomal recessive dihydrorhodamine 123 assay p67phox protein colitis 

Notes

Acknowledgements

Nil.

Compliance with Ethical Standards

Funding

No funding sources for this manuscript.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10875_2016_366_Fig2_ESM.gif (1 kb)
Figure S1

Pedigree of the all three families with A67° CGD- A. The affected child (shown by the arrow) born of non-consanguineous marriage with both the parents being carriers for the mutation c.835_836delAC. The elder brother could not be screened for the carrier status; B. The affected child (shown by arrow) born of non-consanguineous marriage with the mother being carrier for the mutation c.1179–2A>T; C. The affected child (shown by arrow) born of a non-consanguineous marriage with the mother being carrier for the mutation c.835_836delAC. The dihydrorhodamine testing for the elder sister was normal, however, the carrier status has not been screened till date. The mother also had a first-trimester abortion during the second pregnancy (marked as a triangle). The mother’s elder brother had died at day 1 of life. (GIF 765 bytes)

10875_2016_366_MOESM1_ESM.tiff (22 kb)
High resolution image (TIFF 21 kb)
10875_2016_366_MOESM2_ESM.docx (13 kb)
Table S1 (DOCX 13 kb)

References

  1. 1.
    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(6):1319–26. quiz 1327–8CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Roos D, Kuhns DB, Maddalena A, et al. Hematologically important mutations: the autosomal recessive forms of the chronic granulomatous disease (second update). Blood Cells Mol Dis. 2010;44(4):291–9.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Badalzadeh M, Fattahi F, Fazlollahi MR, et al. Molecular analysis of four cases of chronic granulomatous disease caused by defects in NCF-2: the gene encoding the p67-phox. Iran J Allergy Asthma Immunol. 2012;11(4):340–4.PubMedGoogle Scholar
  4. 4.
    Rawat A, Singh S, Suri D, et al. Chronic granulomatous disease: two decades of experience from a tertiary care centre in North West India. J Clin Immunol. 2014;34(1):58–67.CrossRefPubMedGoogle Scholar
  5. 5.
    Noack D, Rae J, Cross AR, et al. Autosomal recessive chronic granulomatous disease caused by novel mutations in NCF-2, the gene encoding the p67-phox component of phagocyte NADPH oxidase. Hum Genet. 1999;105(5):460–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J. 2005;386(3):401–16.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Broides A, Mohammed R, Reid B, Roiffman CM, Grunebaum E. Gastrointestinal abnormalities among patients with chronic granulomatous disease. J Clin Cell Immunol. 2014;5:204.Google Scholar
  8. 8.
    Muise AM, Xu W, Guo C-H, et al. NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut. 2012;61(7):1028–35.CrossRefPubMedGoogle Scholar
  9. 9.
    Schäppi MG, Smith VV, Goldblatt D, Lindley KJ, Milla PJ. Colitis in chronic granulomatous disease. Arch Dis Child. 2001;84(2):147–51.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    de Boer M, Hilarius-Stokman PM, Hossle JP, et al. Autosomal recessive chronic granulomatous disease with absence of the 67-kD cytosolic NADPH oxidase component: identification of mutation and detection of carriers. Blood. 1994;83(2):531–6.PubMedGoogle Scholar
  11. 11.
    Jones LBKR, McGrogan P, Flood TJ, et al. Special article: chronic granulomatous disease in the United Kingdom and Ireland: a comprehensive national patient-based registry. Clin Exp Immunol. 2008;152(2):211–8.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Winkelstein JA, Marino MC, Johnston RB, et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79(3):155–69.CrossRefGoogle Scholar
  13. 13.
    Hagerman A, Rodriguez-Nava V, Boiron P, Crisinel PA, Posfay-Barbe KM. Imipenem-resistant Nocardia cyriacigeorgica infection in a child with chronic granulomatous disease. J Clin Microbiol. 2011;49(3):1185–7.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Dorman SE, Guide SV, Conville PS, et al. Nocardia infection in chronic granulomatous disease. Clin Infect Dis. 2002;35(4):390–4.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Pandiarajan Vignesh
    • 1
  • Amit Rawat
    • 1
  • Ankur Kumar
    • 1
  • Deepti Suri
    • 1
  • Anju Gupta
    • 1
  • Yu L Lau
    • 2
  • Koon W Chan
    • 2
  • Surjit Singh
    • 1
  1. 1.Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Department of PediatricsPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of MedicineThe University of Hong KongHong KongChina

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