Mutations of chronic granulomatous disease in Turkish families

Chronic granulomatous disease (CGD) is an inherited disorder of the innate immune system characterized by impairment of intracellular microbicidal activity of phagocytes. Mutations in one of four known NADPH-oxidase components preclude generation of superoxide and related antimicrobial oxidants, leading to the phenotype of CGD. Defects in gp91-phox, encoded by CYBB, lead to X-linked CGD and have been reported to be responsible for approximately 70% of all CGD cases. The aim of this study was to identify the CGD mutations in a group of Turkish CGD patients and to evaluate the predominance of CGD mutations as X-linked or autosomal recessive (AR) within the Turkish CGD families with known mutations.

Two Turkish CGD families were included in the study, and mutations were identified by sequence analysis of DNA and RNA from peripheral blood in the patients. Before mutation analysis, subgroup analysis of patients was made by flow cytometry with antibodies against NADPH oxidase components and with DHR-123 oxidase activity assay. For comparison, we included previously reported results from four other Turkish CGD families.

Two different mutations were identified, one of them a novel mutation g.700G>T located in exon 7 of CYBB, and the other a hot-spot mutation located in exon 2 of the NCF1 gene. These mutations were detected in three patients from two Turkish families.

Until now, we have altogether identified mutations in six Turkish CGD families. In this limited number of families our results show AR-CGD in two-thirds of the Turkish families investigated, in contrast to previous reports in the literature. This is probably due to the high rate of consanguineous marriages in Turkey. Consanguineous parents were found in 75% of the families with AR-CGD patients, which favours homozygous deficiencies.