title: 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.
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.
authors.affiliation: Chronic Granulomatous Disease Diagnosis and Research Centre, Therex-TIMC/Imag, UMR CNRS 5525, UJF-Grenoble 1, Grenoble, 38041, France. MJStasia@chu-grenoble.fr
authors.forename: Marie José
authors.initials: MJ
authors.lastname: Stasia
authors.forename: Karin
authors.initials: K
authors.lastname: van Leeuwen
authors.forename: Martin
authors.initials: M
authors.lastname: de Boer
authors.forename: Cecile
authors.initials: C
authors.lastname: Martel
authors.forename: Michele
authors.initials: M
authors.lastname: Mollin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Thuret
authors.forename: Gerard
authors.initials: G
authors.lastname: Michel
authors.forename: Celine
authors.initials: C
authors.lastname: Hanson
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Augustine
authors.forename: Charles
authors.initials: C
authors.lastname: Coutton
authors.forename: Véronique
authors.initials: V
authors.lastname: Satre
authors.forename: Carl T
authors.initials: CT
authors.lastname: Wittwer
authors.forename: Harry
authors.initials: H
authors.lastname: Hill
authors.forename: Dirk
authors.initials: D
authors.lastname: Roos
mesh_terms: D000293:Adolescent; D002648:Child; D005091:Exons; D020440:Gene Duplication; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006105:Granulomatous Disease, Chronic / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009154:Mutation; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases