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.
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References
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 1327–8
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.
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.
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.
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.
Groemping Y, Rittinger K. Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J. 2005;386(3):401–16.
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.
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.
Schäppi MG, Smith VV, Goldblatt D, Lindley KJ, Milla PJ. Colitis in chronic granulomatous disease. Arch Dis Child. 2001;84(2):147–51.
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.
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.
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.
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.
Dorman SE, Guide SV, Conville PS, et al. Nocardia infection in chronic granulomatous disease. Clin Infect Dis. 2002;35(4):390–4.
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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)
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Vignesh, P., Rawat, A., Kumar, A. et al. Chronic Granulomatous Disease Due to Neutrophil Cytosolic Factor (NCF2) Gene Mutations in Three Unrelated Families. J Clin Immunol 37, 109–112 (2017). https://doi.org/10.1007/s10875-016-0366-2
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DOI: https://doi.org/10.1007/s10875-016-0366-2