Chronic granulomatous disease of childhood: New polymorphisms in NCF2 gene
Keywords:
primary immunodeficiencies, phagocytes disorders, child, recurrent infectionsAbstract
Objective
Mutations in the NCF2 gene result in the autosomal recessive form of chronic granulomatous disease of childhood. In addition to known mutations, two new substitutions in the NCF2 gene have been described in patients with chronic granulomatous disease of childhood. The objective of this study was to investigate whether these substitutions constitute polymorphisms of the NCF2 gene.
Methods
We investigated the frequency of two substitutions in the NCF2 gene sequence in 214 healthy donors. The first is a C➔ T transition at position -23 of the 5' regulatory region. The second is an A➔G transition at position -21 of the 3' terminal region of intron 1 O. We extracted genomic DNA from peripheral blood cells. The DNA was amplified using PCR with specific primers for the NCF2 gene, analyzed for the presence of single-chain conformational polymorphisms, digested with specific endonucleases and sequenced. The calculation of genotypic and allele frequencies followed the Hardy and Weinberg law.
Results
One hundred individuals were evaluated for the presence of the C➔ T transition at position -23 of the 5' regulatory region; 67% being homozygous for the C allele, 32% heterozygous, and only 1% homozygous for T. One hundred and fourteen individuals were analyzed for the presence of the A➔G transition at position -21 of the 3' terminal region of intron 1 O; of which 36% were homozygous for A, 43% heterozygous and 21% homozygous for G.
Conclusion
Considering the allele frequencies, we conclude that these variants correspond to polymorphisms in the NCF2 gene. Its possible implications on the expression of the NCF2 gene are the subject of current research in our laboratory.
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