Alu-repeat–induced deletions within the NCF2 gene causing p67-phox–deficient chronic granulomatous disease (CGD)
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
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 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.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 151-158 |
Seitenumfang | 8 |
Fachzeitschrift | Human Mutation |
Jahrgang | 31 |
Ausgabenummer | 2 |
Publikationsstatus | Veröffentlicht - Feb. 2010 |
Peer-Review-Status | Ja |
Externe IDs
Scopus | 75149118487 |
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