Novel intronic variant in CYBB causing X-linked chronic granulomatous disease: Case report

Chronic granulomatous disease (CGD) is caused by defective phagocyte NADPH oxidase function, leading to recurrent catalase-positive bacterial and fungal infections, granulomas, and hyperinflammatory manifestations. In some cases of CGD, the identified genetic variant may be novel or discordant with the patient presentation. In these cases, assessment of NADPH oxidase specific protein expression may be beneficial. Here, we present a 16-month-old male presenting with Nocardia and Cutibacterium infection and DHR-based flow cytometry with absent neutrophil oxidative burst. Genetic testing revealed a novel intronic variant in CYBB, so further testing was pursued. The patient had decreased gp91phox and p22phox in neutrophils and monocytes, confirming the diagnosis of X-linked CGD. When available, additional studies, including protein expression and/or functional evaluation can improve genotype-phenotype correlations.