RESUMEN
Chronic granulomatous disease (CGD) is an uncommon inherited disorder of phagocytic cells in which a defective respiratory burst leads to severe recurrent bacterial and fungal infections. The disease is a consequence of mutations in one of the four molecules that constitute the NADPH oxidase system of electron transport, whose most critical component is an unusual flavocytochrome b localized in the plasma and specific granule membranes. Mutations in the CYBB gene (localized in the short arm of the X chromosome) encoding the beta-subunit of this flavocytochrome (gp91-phox), which is are responsible for 60-65% of all cases of CGD. In this paper, we report the molecular characterization of seven unrelated kindreds native from Colombia and Brazil with CGD caused by gp91-phox deficiency. The exons with the possible mutation were identified by single-strand conformational polymorphism (SSCP) of genomic DNA and then confirmed by DNA sequencing. In one patient we found a substitution of A to G in the penultimate nucleotide of intron 12 (IVS12-2A-->G). In four other cases, four different nonsense mutations were detected: R91X, W106X, R157X, and R290X and the other two patients showed missense substitutions: E225V and C244Y. In six of these kindreds, all mothers were carriers but one that did not present any change in the gp91-phox gene, which indicates a de novo mutation in this kindred. Then, these family-specific mutations in gp91-phox produce different structural defects that alter the expression or function of an essential component of phagocyte oxidase.