Rare duplication or deletion of exons 6, 7 and 8 in CYBB leading to X-linked chronic granulomatous disease in two patients from different families.

Chronic granulomatous disease (CGD) is a rare congenital disorder in which phagocytes cannot generate superoxide (O(2)(-)) and other microbicidal oxidants due to mutations in one of the five components of the O(2)(-)-generating NADPH oxidase complex. The most common form is caused by mutations in CYBB on the X chromosome, encoding gp91phox, the enzymatic subunit of the phagocyte NADPH oxidase. Here, we report two rare cases of male X-linked CGD patients, one caused by a 5.7-kb duplication of a region containing CYBB exons 6 to 8 and the other caused by a deletion of this same region. We found both the duplication in patient 1 and the deletion in patient 2 to be bordered by a GT repeat. Indeed, in control DNA, the 3' part of CYBB intron 5 contains a GT repeat and the 5' part of intron 8 also contains such a repeat. Duplication of exons 6, 7 and 8 in patient 1 was probably caused by a non-homologous crossing over between the two GT repeats. The deletion found in patient 2 probably arose from a similar misalignment. The results found in these patients were confirmed by multiplex ligation-dependent probe amplification. The clinical profile of XCGD is severe in both patients.