Introduction: Chronic granulomatous disease (CGD) is a rare inherited condition resulting from mutations in the genes that encode the proteins of the NADPH oxidase enzyme in phagocytes, rendering these cells incapable of killing invading pathogens.
Materials and methods: Patients subtypes are determined by neutrophil functional assays and immunoblotting. Although defects in the X-chromosome-linked gp91-phox component account for the majority of CGD patients in the world, in Iran, there are many CGD patients suffering from the autosomal recessive forms of the disease. Most of these patients show impairment in the synthesis of the 47-kDa cytosolic component p47-phox of the oxidase. The second causative factor of autosomal recessive CGD is deficiency of the 22-kDa component (p22-phox) of the oxidase. Another rare form of the disease is due to mutations in the NCF2 gene encoding the 67-kDa component (p67-phox) of the oxidase.
Results: Mutation analysis showed a novel homozygous splice site mutation, c.intron4+1G>T, in CYBA. A novel mutation in NCF2: a gross homozygous deletion of exon 1 and 2, causing p.Met1_Lys58 deletion in p67-phox. We also found a previously published homozygous nonsense mutation, c.196C>T, causing p.Arg66X.33 in p67-phox.
Discussion: Our data show that CGD in Iran is predominantly due to mutations in p47-phox, while the number of mutations in p22-phox is roughly equal to that in gp91-phox. These data indicate that the genetics of CGD are ethnically variable, and this should be considered in approaching families with CGD.