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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: Publikationen MPI-CBG 2010-arch     Display Documents



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ID: 546731.0, MPI für molekulare Zellbiologie und Genetik / Publikationen MPI-CBG 2010-arch
Alu-repeat-induced deletions within the NCF2 gene causing p67-phox-deficient chronic granulomatous disease (CGD).
Authors:Gentsch, Marcus; Kaczmarczyk, Aneta; Leeuwen, Karin van; Boer, Martin de; Kaus-Drobek, Magdalena; Dagher, Marie-Claire; Kaiser, Petra; Arkwright, Peter D; Gahr, Manfred; Rösen-Wolff, Angela; Bochtler, Matthias; Secord, Elizabeth; Britto-Williams, Pamela; Saifi, Gulam Mustafa; Maddalena, Anne; Dbaibo, Ghassan; Bustamante, Jacinta; Casanova, Jean-Laurent; Roos, Dirk; Roesler, Joachim
Date of Publication (YYYY-MM-DD):2010
Title of Journal:Human Mutation
Volume:31
Issue / Number:2
Start Page:151
End Page:158
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description:Mutations that impair expression or function of the components of the phagocyte NADPH oxidase complex cause chronic granulomatous disease (CGD), which is associated with life-threatening infections and dysregulated granulomatous inflammation. In five CGD patients from four consanguineous families of two different ethnic backgrounds, we found similar genomic homozygous deletions of 1,380 bp comprising exon 5 of NCF2, which could be traced to Alu-mediated recombination events. cDNA sequencing showed in-frame deletions of phase zero exon 5, which encodes one of the tandem repeat motifs in the tetratricopeptide (TPR4) domain of p67-phox. The resulting shortened protein (p67Delta5) had a 10-fold reduced intracellular half-life and was unable to form a functional NADPH oxidase complex. No dominant negative inhibition of oxidase activity by p67Delta5 was observed. We conclude that Alu-induced deletion of the TPR4 domain of p67-phox leads to loss of function and accelerated degradation of the protein, and thus represents a new mechanism causing p67-phox-deficient CGD.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:nn
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:4390
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