Alu-Repeat-Induced Deletions Within the NCF2 Gene Causing p67-phox-Deficient Chronic Granulomatous Disease (CGD)

作者：Gentsch Marcus; Kaczmarczyk Arleta; van Leeuwen Karin; de Boer Martin; Kaus Drobek Magdalena; Dagher Marie Claire; Kaiser Petra; Arkwright Peter D; Gahr Manfred; Roesen 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^*

来源：Human Mutation, 2010, 31(2): 151-158.

DOI：10.1002/humu.21156

• recombination
• immunodeficiency
• phagocyte
• NCF2

Mutations that impair express. ion 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 1,380bp 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-phonx. The resulting shortened protein (p67 Delta 5) 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 p67 Delta 5 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. Hum Mutat 31:151-158, 2010.

• 出版日期2010-2