A novel point mutation in the CYBB gene promoter leading to a rare X minus chronic granulomatous disease variant — Impact on the microbicidal activity of neutrophils

Abstract

This article reports an atypical and extremely rare case of X-linked CGD in an Italian family characterized by a low expression of gp91 phox (X91 − CGD). A novel point mutation in the CYBB gene's promoter (insertion of a T at position − 54T to − 56T) appeared to prevent the full expression of this gene in the patient's neutrophils and correlated with a residual oxidase activity in the whole cells population. The expression and functional activity of the oxidase in eosinophils appeared to be almost normal. Gel shift assays indicated that the mutation led to decreased interactions with DNA-binding proteins. The total O 2 − production in the patient's granulocytes (5–7% of normal) supported no microbicidal power after 45 min and 60 min of contact with S. aureus and C. albicans, respectively. Despite this residual oxidase activity, the patients suffered from severe and life-threatening infections. It was concluded that in these X91 − CGD neutrophils, the O 2 − production per se was not sufficient to protect the patient against severe infections.