![]() ![]() Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA. Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome. Wada T, Yasui M, Toma T, Nakayama Y, Nishida M, Shimizu M, et al. Frameshift indels introduced by genome editing can lead to in-frame exon skipping. Lalonde S, Stone OA, Lessard S, Lavertu A, Desjardins J, Beaudoin M, et al. Alternative translation start sites and hidden coding potential of eukaryotic mRNAs. Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome. ![]() Kotlarz D, Zietara N, Uzel G, Weidemann T, Braun CJ, Diestelhorst J, et al. Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15. Ring AM, Lin JX, Feng D, Mitra S, Rickert M, Bowman GR, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, et al. Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors. Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy. Kotlarz D, Marquardt B, Baroy T, Lee WS, Konnikova L, Hollizeck S, et al. Atypical X-linked severe combined immunodeficiency due to possible spontaneous reversion of the genetic defect in T cells. Stephan V, Wahn V, Le Deist F, Dirksen U, Broker B, Muller-Fleckenstein I, et al. Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency. Speckmann C, Pannicke U, Wiech E, Schwarz K, Fisch P, Friedrich W, et al. Patients with T(+)/low NK(+) IL-2 receptor gamma chain deficiency have differentially-impaired cytokine signaling resulting in severe combined immunodeficiency. 2000 122:143–9.įuchs S, Rensing-Ehl A, Erlacher M, Vraetz T, Hartjes L, Janda A, et al. Severe combined immunodeficiencies (SCID). Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, et al. New insights into the regulation of T cells by gamma(c) family cytokines. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. 1997 130:378–87.įelgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. 1993 123:564–72.īuckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, et al. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. Stephan JL, Vlekova V, Le Deist F, Blanche S, Donadieu J, De Saint-Basile G, et al. Mutations in genes required for T-cell development: IL7R, CD45, IL2RG, JAK3, RAG1, RAG2, ARTEMIS, and ADA and severe combined immunodeficiency: HuGE review. Kalman L, Lindegren ML, Kobrynski L, Vogt R, Hannon H, Howard JT, et al. Confounding effects of alternative splicing may partially rescue genetic defects and should be considered in patients with inborn errors of immunity. Thus, our study shows that IL2RG deficiency can be associated with differential signaling defects. In silico modeling suggested that the IL-2Rγ mutation reduces the stabilization of IL-4 and IL-21 cytokine binding by affecting the N-terminal domain of the IL-2Rγ. Examination of RNA isoforms detected alternative splicing downstream of IL2RG exon 1 in both patients resulting in resolution of the predicted frameshift and 16 mutated amino acids. While IL-2, IL-7, and IL-15 signaling showed only mild defects of STAT5 phosphorylation in response to the respective cytokines, IL-4- and IL-21-induced phosphorylation of STAT3 and STAT6 was markedly reduced. However, flow cytometry revealed normal surface expression of the IL-2Rγ chain. Using whole exome sequencing, we identified a base pair deletion in the first exon of IL2RG predicted to cause a frameshift and premature stop. Pan T, B, and NK cell numbers were normal, but immunophenotyping revealed defective B cell differentiation. Here, we report two brothers suffering from chronic cryptosporidiosis, severe diarrhea, and cholangitis. Inborn errors in interleukin 2 receptor, gamma ( IL2RG) perturb signaling of the common gamma chain family cytokines and cause severe combined immunodeficiency (SCID). ![]()
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