title: Determination of the deletion breakpoints in two patients with contiguous gene syndrome encompassing CYBB gene.
abstract: X-linked chronic granulomatous disease is a primary immunodeficiency caused by mutations in CYBB. Although large deletions involving CYBB are known to cause contiguous gene syndrome (CGS), only a few patients have been studied precisely at the molecular levels. Our study determined the deletion breakpoints in two patients with CGS involving CYBB by array comparative genomic hybridization and the following PCR and DNA walking studies. The deletion size was 3.5 Mb in Patient 1 and 0.8 Mb in Patient 2. There were no homologous architectural features between the telomeric and centromeric breakpoint junctions in the deletions of either patient. However, the telomeric breakpoint of Patient 2 was embedded in a stretch of low-copy repeats and the centromeric breakpoint was also embedded in a stretch of short segments with significant sequence homology. These findings suggest the potential involvement of genome architecture in stimulating genomic rearrangements in Patient 2.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku Sapporo 060-8638, Japan. yamadam@med.hokudai.ac.jp
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamada
authors.forename: Takashi
authors.initials: T
authors.lastname: Arai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Oishi
authors.forename: Norikazu
authors.initials: N
authors.lastname: Hatano
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kobayashi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Kubota
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Minami
authors.initials: M
authors.lastname: Yoda
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kawamura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D055028:Comparative Genomic Hybridization; D017353:Gene Deletion; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics*; D056916:Segmental Duplications, Genomic / Q000235:genetics; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases