Erschienen in:
01.08.2012
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
verfasst von:
Marie José Stasia, Karin van Leeuwen, Martin de Boer, Cecile Martel, Michele Mollin, Isabelle Thuret, Gerard Michel, Celine Hanson, Nancy H. Augustine, Charles Coutton, Véronique Satre, Carl T. Wittwer, Harry Hill, Dirk Roos
Erschienen in:
Journal of Clinical Immunology
|
Ausgabe 4/2012
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Abstract
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.