LETTER TO EDITOR Chronic Granulomatous Disease Due to Neutrophil Cytosolic Factor (NCF2) Gene Mutations in Three Unrelated Families 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 Received: 10 November 2016 /Accepted: 20 December 2016 # Springer Science+Business Media New York 2016 Abstract Chronic granulomatous disease (CGD) is an inher- itable 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 find- ings 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 To the Editor: Chronic granulomatous disease (CGD) is an inheritable func- tional phagocytic disorder resulting from defects in one of the several components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. CGD is inherited in both an X-linked and an autosomal recessive fashion depend- ing on the underlying gene defects. X-linked CGD is due to mutations in the CYBB gene whereas autosomal recessive form results due to mutations in CYBA, NCF1, NCF2, and NCF4 genes [1]. Autosomal recessive CGD (AR-CGD) due to mutations in the NCF2 gene accounts for less than 5% of cases of CGD and has not been reported previously from India [2]. We report three unrelated families with mutations in the NCF2 as the cause of CGD in the affected children [Table 1]. Case Details Case 1 A 2-year-old boy, a resident of Kapurthala (district), Punjab (state), who was born of a non-consanguineous mar- riage was referred to us for chronic febrile illness with cough of 1 month duration. He had been ill since 6 weeks of life with recurrent lymphadenitis and recurrent skin abscesses. At 1.5 years, he had an episode of fulminant colitis requiring one unit of blood transfusion. The colitis resolved with anti- biotics and there was no recurrence of colitis after that epi- sode. His family history was unremarkable. The child ap- peared wasted and stunted for his age and had bilateral pneu- monia and firm hepatosplenomegaly at presentation. Laboratory investigations revealed polymorphonuclear leucocytosis, microcytic anemia, and thrombocytosis with el- evated inflammatory markers. His blood cultures were sterile and fungal serology was positive for Aspergillus flavus and Candida albicans. Hypergammaglobulinemia was noted and nitroblue tetrazolium (NBT) reduction testing showed no Electronic supplementary material The online version of this article (doi:10.1007/s10875-016-0366-2) contains supplementary material, which is available to authorized users. * Amit Rawat rawatamit@yahoo.com 1 Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India 2 Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong Special Administrative Region, China J Clin Immunol DOI 10.1007/s10875-016-0366-2