Background: One of the rarest forms of autosomal recessive chronic granulomatous disease (AR-CGD) is attributable to mutations in the CYBA gene, which encodes the alpha polypeptide of cytochrome b(558), (also known as p22-phox), a key transmembrane protein in the phagocyte NADPH oxidase system. This gene is localized on chromosome 16q24, encompasses 8.5 kb and contains six exons.
Materials and methods: We report here the clinical and molecular characterization of 12 AR-CGD patients from 10 consanguineous, unrelated Turkish families with clinical CGD and positive family history. The ages of the six male and six female patients were between 1and 18 years. Before mutation analysis, subgroup analysis of patients was made by flow cytometry with antibodies against NADPH-oxidase components and with the DHR assay (flow cytometric assay of NADPH oxidase activity in leucocytes).
Results: Mutation analysis of CYBA showed six different mutations: a frameshift insertion in exon 3 (C after C166); a missense mutation in exon 2 (p.Gly24Arg), a splice-site deletion in intron 1 (4-bp deletion +4_+7 AGTG), a novel nonsense mutation in exon 6 (p.Cys113X), a novel large deletion of exons 3-6 and a novel 1-bp deletion in exon 6 (c.408delC). All mutations were present in homozygous form and all parents investigated were found to be heterozygotes for these mutations.
Conclusions: In our series of 40 CGD families, approximately 25% of the families have p22-phox defects, with six different mutations, including three novel mutations. The high rate of consanguineous marriages seems to be the underlying aetiology.