An unusual intronic mutation in the CYBB gene giving rise to chronic granulomatous disease

The most common, X-linked, form. of chronic granulomatous disease (CGD) is caused by mutations in the CYBB gene located at Xp21.1. The product of this gene is the large subunit of flavocytochrome b(558), gp91(phox), which for ms the catalytic core of the antimicrobial superoxide-generating enzyme, NA DPH oxidase. In the overwhelming majority of cases, mutations are family-sp ecific and occur in the exonic regions of the gene, or more rarely at the i ntron/exon borders. Alternatively, they are large (often multi-gene) deleti ons. In addition, four mutations have been found in the promoter region. In contrast, very few intronic mutations have been reported. Here we describe an intronic mutation that causes X-linked CGD. A single nucleotide substit ution in the middle of intron V creates a novel 5' splice site and results in multiple abnormal mRNA products. (C) 2001 Elsevier Science B.V. All righ ts reserved.