The p47-phox Pseudogene and Chronic Granulomatous Disease A p47-phox Pseudogene Carries the Most Common Mutation Causing p47-phox -deficient Chronic Granulomatous Disease

Abstract

Abstract The predominant genetic defect causing p47-phox -deficient chronic granulomatous disease (A47 Њ CGD) is a GT deletion ( ⌬ GT) at the beginning of exon 2. No explanation exists to account for the high incidence of this single mutation causing a rare disease in an unrelated, racially diverse population. In each of 34 consecutive unrelated normal individuals, both the normal and mutant ⌬ GT sequences were present in genomic DNA, suggesting that a p47-phox related sequence carrying ⌬ GT exists in the normal population. Screening of genomic bacteriophage and YAC libraries identified 13 p47-phox bacteriophage and 19 YAC clones. The GT deletion was found in 11 bacteriophage and 15 YAC clones. Only 5 exonic and 33 intronic differences distinguished all ⌬ GT clones from all wild-type clones. The most striking differences were a 30-bp deletion in intron 1 and a 20-bp duplication in intron 2. These results provide good evidence for the existence of at least one highly homologous p47-phox pseudogene containing the ⌬ GT mutation