Alu-repeat-induced deletions within the NCF2 gene causing p67-phox-deficient chronic granulomatous Disease (CGD)

Marcus Gentsch, Aneta Kaczmarczyk, Karin Van Leeuwen, Martin De Boer, Magdalena Kaus-Drobek, Marie Claire Dagher, Petra Kaiser, Peter D. Arkwright, Manfred Gahr, Angela Rösen-Wolff, Matthias Bochtler, Elizabeth Secord, Pamela Britto-Williams, Gulam Mustafa Saifi, Anne Maddalena, Ghassan Dbaibo, Jacinta Bustamante, Jean Laurent Casanova, Dirk Roos, Joachim Roesler

    Research output: Contribution to journalArticlepeer-review


    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 (p67Δ5) 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 p67Δ5 was observed. We conclude that Aluinduced 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. © 2009 Wiley-Liss, Inc.
    Original languageEnglish
    Pages (from-to)151-158
    Number of pages7
    JournalHuman Mutation
    Issue number2
    Publication statusPublished - Feb 2010


    • Immunodeficiency
    • NCF2
    • Phagocyte
    • Recombination


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