Chronic granulomatous disease (CGD) is a rare congenital disorder of the innate immune system. CGD is caused by a defect in any one of four components of the NADPH oxidase, i.e. gp91phox, p22phox, p47phox or p67phox. Most CGD patients (~65%) from Western populations have a mutation in CYBB coding gp91phox, and some (~30%) have a mutation in NCF1. We screened X linked CGD gene to detect mutation in this male patient.
We have used flow cytometry for functional diagnosis and subgroup identification of X-CGD case whose mother is a carrier having bimodal histogram pattern in DHR assay and p22 intracelulary subgroup analysis, since gp91phox and p22 coexisting. To detect mutation we used next generation sequencing of CYBB gene mutations.
The 5 year old male patient suffered due to recurrent necrotising pneumonia and widespread lypmhadenopathy after routinely applied BCG vaccination. The clinical features signified immun deficiency in particular CGD, respectively. DHR analysis showed no oxidase activitiy in neutrophils but surprisingly normal activity in eosinophils. Mother's DHR showed bimodal pattern. In total being a male and mother is a carrier we suspected CYBB gene. NGS resulted as a novel mutation in the promoter region c.-65C>G.
X-CGD patients with promotor mutations in CYBB is rare.NGS is a good method to detect mutations not in the exons.
The clinical phenotypes can vary.Promoter mutations are assumed to have with milder phenotype and late diagnose but our case is contradictory. Although eosinophils have almost normal oxidase activiy it is not enough for effective microbial killing.