An in‐frame triplet deletion within the gp91‐phox gene in an adult X‐linked chronic granulomatous disease patient with residual NADPH–oxidase activity

Abstract

In an adult patient suffering from X‐linked chronic granulomatous disease (X‐CGD) with residual activity of the NADPH–oxidase we found an unusual biochemical constellation with a defective gp91‐phox gene. As shown by Western blot using a specific antibody the gp91‐phox protein was normal in PMN. However, NADPH–oxidase activity was reduced and no heme spectrum was detectable. By Southern blot and RFLP analysis of genomic DNA a larger defect within the gp91‐phox gene was excluded. Sequencing of the gp91‐phox cDNA revealed an in‐frame deletion of a TTC triplet 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 propositus confirmed this mutation. The absence of a functional cytochrome b558‐spectrum in granulocytes of the patient suggests an involvement 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 functional cytochrome b558‐spectrum but with detectable gp91‐phox protein and residual NADPH‐oxidase activity.

Residual NADPH Oxidase Activity and Isolated Lung Involvement in X-Linked Chronic Granulomatous Disease

“…For instance, Brunner et al reported an X-linked CGD case with partially preserved oxidase activity and sarcoidosis-like picture caused by an intraexonic splice defect in the gene encoding gp91-phox (CYBB exon 3, c.262G->A) [12]. Another X-linked case with residual NADPH oxidase activity (in-frame triplet deletion in gp91-phox gene) was seen in an adult with multisystem disease that included staphylococcal lymphadenitis, recurrent pneumonia, and liver/renal abscesses [13]. Similarly, a gp91-phox gene splice site mutation (5′intron3 GTAAG/GTAAA), with residual NADPH, was described in a 40-year-old man with liver abscesses ( Staphylococcus aureus ) and septicemia ( Salmonella enteritis ) [14].…”