AN IN-FRAME TRIPLET DELETION WITHIN THE GP91-PHOX GENE IN AN ADULT X-LINKED CHRONIC GRANULOMATOUS-DISEASE PATIENT WITH RESIDUAL NADPH-OXIDASE ACTIVITY

In an adult patient suffering from X-linked chronic granulomatous dise ase (X-CGD) with residual activity of the NADPH-oxidase we found an un usual biochemical constellation with a defective gp91-phox gene. As sh own by Western blot using a specific antibody the gp91-phox protein wa s normal in PMN. However, NADPH-oxidase activity was reduced and no he me spectrum was detectable. By Southern blot and RFLP analysis of geno mic DNA a larger defect within the gp91-phox gene was excluded. Sequen cing of the gp91-phox cDNA revealed an in-frame deletion of a TTC trip let in exon VI of the gp91-phox gene. This mutation indicates the loss of one amino acid (phenylalanine 215 or 216) in the gp91-phox protein . Sequencing of genomic DNA from the heterozygous daughter of the prop ositus confirmed this mutation. The absence of a functional cytochrome b(588)-spectrum in granulocytes of the patient suggests an involvemen t of the phenylalanine 216 area in heme binding by gp91-phox. This is the first mutation described in a X-CGD patient with absence of a func tional cytochrome b(558)-spectrum but with detectable gp91-phox protei n and residual NADPH-oxidase activity.