title: A 1.1-kb duplication in the p67-phox gene causes chronic granulomatous disease.
abstract: Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency that is caused by a functional defect of the NADPH oxidase of phagocytes, and that leads to severe recurrent infections. CGD results from the absence or the dysfunction of various components of NADPH oxidase, and autosomal recessive CGD with the lack of p67-phox (A67 CGD) is the rarest form of the disease. Identifying familiar mutations in subjects with A67 CGD provides the most reliable method of detecting carriers and is the basis for prenatal diagnosis. In the present study, we report the detailed characterization of the first duplication in the p67-phox gene identified in a 30-year-old patient affected by systemic aspergillosis attributable to p67-phox deficiency. We show that this new mutation involving exons 9 and 10 is the result of a tandem duplication of approximately 1.1 kb, which resulted from the juxtaposition of intron 8 to intron 10. We have sequenced both the junction fragment of this duplication and the corresponding wild-type regions and have found that the breakpoint regions in intron 8 and in intron 10 show limited homology. Our result suggests that this interchange arose as an illegitimate recombination event. As in other non-homologous rearrangements previously reported, the duplication breakpoints are located within the sequence motif 5'-CCAG-3' and its complement 5'-CTGG-3'.
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Verona, Policlinico GB Rossi, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Borgato
authors.forename: A
authors.initials: A
authors.lastname: Bonizzato
authors.forename: C
authors.initials: C
authors.lastname: Lunardi
authors.forename: S
authors.initials: S
authors.lastname: Dusi
authors.forename: G
authors.initials: G
authors.lastname: Andrioli
authors.forename: A
authors.initials: A
authors.lastname: Scarperi
authors.forename: R
authors.initials: R
authors.lastname: Corrocher
mesh_terms: D000328:Adult; D001483:Base Sequence; D003241:Consanguinity; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D020440:Gene Duplication; D006105:Granulomatous Disease, Chronic / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
chemical_list: D010750:Phosphoproteins; D012333:RNA, Messenger; C079789:neutrophil cytosol factor 67K; D004247:DNA