DETECTION OF GP91-PHOX PRECURSOR PROTEIN IN B-CELL LINES FROM PATIENTS WITH X-LINKED CHRONIC GRANULOMATOUS-DISEASE AS AN INDICATOR FOR MUTATIONS IMPAIRING CYTOCHROME B(558) BIOSYNTHESIS

NADPH oxidase cytochrome b(558) consists of two subunits, gp91-phox an d p22-phox, defects of which result in chronic granulomatous disease ( CGD). The nature of the interaction between these subunits has yet to be determined. Absence of p22-phox in autosomal CGD patient-derived B- cell lines results in detectable levels of an incompletely glycosylate d gp91-phox precursor. We have detected this same precursor species in four cell lines from patients with the X-linked form of the disease d ue to mutations in gp91-phox. Such mutations should delineate regions of gp91-phox important for its biosynthesis, including stable associat ion with p22-phox. One mutation mapped to the putative FAD-binding dom ain, one mapped to a potential haem-binding domain, and two involved t he region encoded by exon 3.