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Updated: Jul 14, 2026

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
GvHD-associated cytokine polymorphisms do not associate with Omenn syndrome rather than T-B- SCID in patients with
Iram J Haq1, Laura J Steinberg, Manfred Hoenig
1Institute of Cellular Medicine, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Abstract:
Recombinase activating genes 1/2 (RAG1/2) deficiency, critical to initiate gene rearrangement encoding lymphocyte receptors, causes T-B- severe combined immunodeficiency (SCID) and Omenn syndrome (OS), characterised by erythroderma, hepatosplenomegaly, lymphadenopathy, activated, clonal T cell expansions with restricted TCRVbeta family usage, and opportunistic infection. Many features of OS resemble graft-versus-host disease (GvHD). Frequency of GvHD-associated cytokine gene polymorphisms (CGPs) with OS was investigated to explain phenotypic differences between T-B- SCID and OS. Allele frequencies of IFNgamma T874A, IFNgamma-R1, TNFalphad microsatellites, IL-10 promoter region C592A and A1082G, IL-4 C-590T, IL-6 G-174C, IL-4R Q+576R, IFNgamma-R1 T-56C, TNFalphaRII 196 M/R single-nucleotide polymorphisms and IL-1Ra intron 1 VNTR were examined in 33 OS and 23 SCID patients. No significant differences in allele frequencies were found between the groups, and no trends identified. The mechanisms determining the OS or T-B-NK+ SCID phenotype remain to be determined.
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