CDiReC - Chronic Granulomatous Disease (CGD) Diagnosis and Research Center

Centre Diagnostic et Recherche sur la CGD (Granulomatose Septique Chronique)

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What is the biological defect of CGD ?

Phagocytic leukocytes are essential cells of the innate immune system that have to rapidly respond to invading microbes and fight them like infantrymen in an army. The responses of phagocytes to pathogens include phagocytosis, proteolytic destruction within granules, damage induced by superoxide, and reactive oxygen species (ROS) generated by membranous nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Primary phagocytic defects must be included in the differential diagnosis of life-threatening and recurrent infections and fever in children and occasionally in adults.

NADPH oxidase complex

Figure 1: Different CGD forms involving one of the
four genes encoding the proteins of the NADPH
oxidase complex

The central importance of the phagocyte NADPH oxidase to innate host defense is illustrated in chronic granulomatous disease (CGD), a rare genetic disorder (estimated prevalence of 1/250,000 to 1/200,000) characterized by severe and recurrent infections due to the inability of phagocytes to mount a respiratory burst to kill invading bacteria and fungi.

CGD results from the failure of the NADPH oxidase activity in phagocytes. Genetically, CGD is a heterogeneous disease caused by mutations in any of four proteins of the NADPH oxidase complex, including NOX2, p22phox, both subunits of the membranous cytochrome b558, p47phox, and p67phox, the cytosolic components of this enzyme The X-linked recessive transmission type of CGD (XCGD), characterized by mutations in the CYBB gene encoding NOX2, is the most frequent form of CGD (approximately 60% of cases).

The second most common form of CGD is autosomal recessive (ARCGD), accounting for approximately 30% of the cases, which most of the time is caused by the deletion of a GT from a GTGT tandem repeat at the first splice junction in the NCF1 gene encoding p47phox (AR470 CGD). In addition to these usual CGD types, mutations in the CYBA and NCF2 genes encoding p22phox and p67phox, respectively, account for rare AR220 CGD and AR670 CGD, each accounting for less than 5% of cases.

  Directeur de publication:  Marie-José Stasia   Webmaster:   Marie-Claire Dagher  Last update:  February, 25, 2009