Identification of a novel NCF-1 (p47-phox) pseudogene not containing the signature GT deletion: significance for A47° chronic granulomatous disease carrier detection

Abstract

The p47-phox gene, NCF-1, has 2 nearly identical pseudogenes (NCF-1) in proximity at chromosomal locus 7q11.23. A dinucleotide deletion (⌬GT) at the beginning of exon 2 that leads to a frameshift and premature stop codon is considered the signature sequence of the pseudogenes. It is also the most prevalent mutation in p47-phox-deficient (A47°) chronic granulomatous disease (CGD) as a result of the insertion of a ⌬GT-containing fragment of pseudogene into NCF-1. Extending our study of the relationship between NCF-1 and NCF-1 to 53 unaffected control individuals, we found that although in most (n ‫؍‬ 44), the ratio of pseudogene (⌬GT) to functional gene (GTGT) sequence in amplicons spanning exon 2 was 2:1, as previously observed, surprisingly, in 7 persons the ratio was 1:1, and in 2 persons the ratio was 1:2. The lowered ratios are explained by the presence, in a heterozygous or homozygous state, respectively, of a pseudogene that contains GTGT rather than ⌬GT.

Chronic granulomatous disease caused by mutations other than the common GT deletion inNCF1, the gene encoding the p47phoxcomponent of the phagocyte NADPH oxidase

“…Similar methods were published by Heyworth et al [2002], based on nucleotide peak heights or on radioactivity incorporated in such PCR products. The limitation of these methods is that they only determine the ratio between the number of NCF1 and cNCF1 genes, but do not give information on the real number of these genes in the genome.…”

“…Nevertheless, these methods are useful to detect the presence of GTGT-containing NCF1 gene(s) in A471 CGD patients. For carrier detection, however, these methods are not always completely reliable [Heyworth et al, 2002].…”

Association between p47phox pseudogenes and inflammatory bowel disease

“…We read with great interest the recent article by Heyworth et al, 1 which describes the ratio between the p47 phox pseudogenes (NCF1) and the p47 phox gene (NCF1). Gene duplication has prevented elucidation of the genomic sequence at 7q11.23, although the NCF1/NCF1 ratio had been assumed 2-4 to be 2:1.…”

Detection of arthritis‐susceptibility loci, including Ncf1, and variable effects of the major histocompatibility complex region depending on genetic background in rats

“…These genetic interactions could partially explain why it has been challenging to study the genetic association of NCF1 in human RA, and the E3.DA-congenic rat might be an excellent tool to identify those loci. However, another reason why conducting association studies of NCF1 has been a difficult task is the high complexity of the human NCF1 region, with 2 nonfunctional pseudogenes and evidence of an additional functional copy, all of which are in close proximity to NCF1 (29).…”