Point mutations in the promoter region of the CYBB gene leading to mild chronic granulomatous disease

Chronic granulomatous disease (CGD) is a clinical syndrome of recurrent bac terial and fungal infections caused by a rare disorder of phagocytic cells. In CGD, the phagocytes are unable to generate oxygen radicals after stimul ation of these cells, due to a defect in the NADPH oxidase system. This NAD PH oxidase is a multicomponent enzyme of at least four subunits, of which t he beta -subunit of cytochrome b(558), gp91-phox, is encoded by an X-linked gene (called CYBB). We report here five patients from two families; in eac h family we found a different mutation in the promoter region of CYBB. Both mutations prevented the expression of gp91-phox in the patients' neutrophi ls and thus caused inability of these cells to generate oxygen radicals. Ho wever, the mutations left the gp91-phox expression and the function of the NADPH oxidase in the patients' eosinophils intact. The relatively mild cour se of the CGD in these patients can probably be attributed to the fact that the eosinophils have retained their oxidative capacity. Furthermore, our r esults indicate that neutrophils and eosinophils differ in their regulation of gp91-phox expression.