A novel mutation in the CYBB gene resulting in an unexpected pattern of exon skipping and chronic granulomatous disease

Chronic granulomatous disease is a rare inherited disorder caused by non-ex istent or severely decreased phagocyte superoxide production that results i n a severe defect in host defense and consequent predisposition to microbia l infection. The enzyme responsible for superoxide production, NADPH oxidas e, involves at least five components. An absence of, or a defect in, any on e of four of these proteins (p47(phox), p67(phox), p22(phox) and gp91(phox) ) gives rise to the known types of chronic granulomatous disease. The most common form of inheritance is X-linked and is due to mutations in the CYBB gene that encodes gp91(phox), the large subunit of flavocytochrome b, the t erminal electron donor of the oxidase. we have recently reported a large nu mber of mutations in this gene revealing a broad range of defects, includin g large and small deletions, and frameshift, nonsense, missense, splice reg ion and regulatory region mutations. Here we report a patient who has an un usual type of mutation that results in the generation of a 'pseudo-exon' in the gp91(phox) mRNA and an unexpected pattern of splicing. (C) 1999 Elsevi er Science B.V. All rights reserved.