A p47-phox pseudogene carries the most common mutation causing p47-phox- deficient chronic granulomatous disease.

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.

Rapid Detection of Intracellular p47phox and p67phox by Flow Cytometry; Useful Screening Tests for Chronic Granulomatous Disease

“…However, the vast majority of patients with p47phox deficiency carry the homozygous 2-bp deletion in the NCF1 gene, which was also detected in our patients. This mutation results from recombination events between the wild-type gene and the pseudogene [22,23]. Patients with this mutation have been reported to exhibit undetectable levels of p47phox protein expression [23], which was consistent with our results.…”

PU.1 Is Essential for p47 Promoter Activity in Myeloid Cells

“…These authors suggested that recombination between the wild type p47 phox gene and its pseudogene is the main cause of the autosomal recessive form of chronic granulomatous disease associated with absence of p47 phox protein. The intron-exon structures of the wild type and pseudogene are identical, they are similarly transcribed and there are no major differences in their proximal promoter regions (68). Our new data are compatible with this observation.…”

“…Recently, Gorlach et al (68) reported a p47 phox pseudogene that is highly homologous to the gene itself, with the notable exception of a GT deletion at the beginning of exon 2 leading to a frameshift and premature stop codon. These authors suggested that recombination between the wild type p47 phox gene and its pseudogene is the main cause of the autosomal recessive form of chronic granulomatous disease associated with absence of p47 phox protein.…”

The genomic basis of the Williams – Beuren syndrome

“…The centromeric and the telomeric part contain gene copies of NCF1, which are expressed as truncated proteins with a very short open reading frame (ORF). Homozygous or compound-heterozygous mutations of this gene cause one form of chronic granulomatous disease, a rare disorder with multi-organ manifestation due to an immunodeficiency [89,134,135]. Recent findings suggest a contribution of NCF1 to the development of hypertension.…”