File(s) not publicly available
A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection
journal contribution
posted on 2023-06-08, 17:15 authored by Melanie NewportMelanie Newport, Clare M Huxley, Sara Huston, Catherine M Hawrylowicz, Ben A Oostra, Robert Williamson, Michael LevinBACKGROUND Genetic differences in immune responses may affect susceptibility to mycobacterial infection, but no specific genes have been implicated in humans. We studied four children who had an unexplained genetic susceptibility to mycobacterial infection and who appeared to have inherited the same recessive mutation from a common ancestor. METHODS We used microsatellite analysis, immunofluorescence studies, and sequence analysis to study the affected patients, unaffected family members, and normal controls. RESULTS A genome search using microsatellite markers identified a region on chromosome 6q in which the affected children were all homozygous for eight markers. The gene for interferon-gamma receptor 1 maps to this region. Immunofluorescence studies showed that the receptor was absent on leukocytes from the affected children. Sequence analysis of complementary DNA for the gene for interferon-gamma receptor 1 revealed a point mutation at nucleotide 395 that introduces a stop codon and results in a truncated protein that lacks the transmembrane and cytoplasmic domains. CONCLUSIONS Four children with severe mycobacterial infections had a mutation in the gene for interferon-gamma receptor 1 that leads to the absence of receptors on cell surfaces and a functional defect in the up-regulation of tumor necrosis factor alpha by macrophages in response to interferon-gamma. The interferon-gamma pathway is important in the response to intracellular pathogens such as mycobacteria.
History
Publication status
- Published
Journal
New England Journal of MedicineISSN
0028-4793Publisher
Massachusetts Medical SocietyExternal DOI
Issue
26Volume
335Page range
1941-1949Department affiliated with
- Global Health and Infection Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2014-05-13Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC