Abstract
Abstract
X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations of the gene for the γ-chain (γc) of the interleukin-2 receptor, IL2RG. We analyzed the clinical, immunologic, and molecular characteristics of children with X-SCID, attempting to improve the diagnosis and treatment of X-SCID in China.
Methods
X-SCID was suspected in male infants with recurrent or persistent infections. Eleven male infants from ten unrelated Chinese families were included. The IL2RG gene was amplified and sequenced, followed by mutation analysis in these children and their female relatives. X-linked short tandem repeat (X-STR) typing was done to define the maternal lymphocyte engraftment.
Results
The 11 children exhibited recurrent infections and 10 of them had lymphopenia. B cells were present in all patients, T cells were markedly reduced in 10, and NK cells were markedly reduced in 9. Nine IL2RG gene mutations were identified in the 11 children, with 5 novel mutations. One patient was found to have the maternal lymphocyte engraftment.
Conclusion
The clinical presentations and immunologic characteristics of the X-SCID patients were accordingly quite uniform despite the heterogeneity of mutations locating almost in the entire γc gene.
Similar content being viewed by others
References
Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr 1997;130:378–387.
Primary immunodeficiency diseases. Report of a WHO scientific group. Immunodefic Rev 1992;3:195–236.
Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 1999;340:508–516.
Kovanen PE, Leonard WJ. Cytokines and immunodeficiency diseases: critical roles of the gamma(c)-dependent cytokines interleukins 2, 4, 7, 9, 15, and 21, and their signaling pathways. Immunol Rev 2004;202:67–83.
Sugamura K, Asao H, Kondo M, Tanaka N, Ishii N, Ohbo K, et al. The interleukin-2 receptor gamma chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol 1996;14:179–205.
Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, et al. Long-term survival and transplantation of hemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. Lancet 2003;361:553–560.
Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol 2004;22:625–655.
Baker MW, Laessig RH, Katcher ML, Routes JM, Grossman WJ, Verbsky J, et al. Implementing routine testing for severe combined immunodeficiency within Wisconsin’s newborn screening program. Public Health Rep 2010;125Suppl 2:88–95.
Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, et al. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood 1997;89:1968–1977.
Kanai N, Yanai F, Hirose S, Nibu K, Izuhara K, Tani T, et al. A G to A transition at the last nucleotide of exon 6 of the gamma c gene (868G—>A) may result in either a splice or missense mutation in patients with X-linked severe combined immunodeficiency. Hum Genet 1999;104:36–42.
Chen YJ, Chen F, Xin N, Zhang HB, Zheng HB, Yu B, et al. Genetic polymorphisms of X-STR loci in Chinese Yugur ethnic group and its application. Yi Chuan 2008;30:1143–1152. [In Chinese]
Kam KM, Leung WL, Wong KH, Lee SS, Hung MY, Kwok MY. Maturational changes in peripheral lymphocyte subsets pertinent to monitoring human immunodeficiency virusinfected Chinese pediatric patients. Clin Diagn Lab Immunol 2001;8:926–931.
Lin SC, Chou CC, Tsai MJ, Wu KH, Huang MT, Wang LH, et al. Age-related changes in blood lymphocyte subsets of Chinese children. Pediatr Allergy Immunol 1998;9:215–220.
Stephan JL, Vlekova V, Le Deist F, Blanche S, Donadieu J, De Saint-Basile G, et al. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr 1993;123:564–572.
Toida I, Nakata S. Severe adverse reactions after vaccination with Japanese BCG vaccine: a review. Kekkaku 2007;82:809–824.
Gossage DL, Buckley RH. Prevalence of lymphocytopenia in severe combined immunodeficiency. N Engl J Med 1990;323:1422–1423.
Hague RA, Rassam S, Morgan G, Cant AJ. Early diagnosis of severe combined immunodeficiency syndrome. Arch Dis Child 1994;70:260–263.
O’Reilly RJ, Keever CA, Small TN, Brochstein J. The use of HLA-non-identical T-cell-depleted marrow transplants for correction of severe combined immunodeficiency disease. Immunodefic Rev 1989;1:273–309.
Niemela JE, Puck JM, Fischer RE, Fleisher TA, Hsu AP. Efficient detection of thirty-seven new IL2RG mutations in human X-linked severe combined immunodeficiency. Clin Immunol 2000;95:33–38.
Maquat LE. When cells stop making sense: effects of nonsense codons on RNA metabolism in vertebrate cells. RNA 1995;1:453–465.
Frischmeyer PA, Dietz HC. Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 1999;8:1893–1900.
Puck JM, Deschênes SM, Porter JC, Dutra AS, Brown CJ, Willard HF, et al. The interleukin-2 receptor gamma chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet 1993;2:1099–1104.
Ishii N, Asao H, Kimura Y, Takeshita T, Nakamura M, Tsuchiya S, et al. Impairment of ligand binding and growth signaling of mutant IL-2 receptor gamma-chains in patients with X-linked severe combined immunodeficiency. J Immunol 1994;153:1310–1317.
Ting SS, Leigh D, Lindeman R, Ziegler JB. Identification of X-linked severe combined immunodeficiency by mutation analysis of blood and hair roots. Br J Haematol 1999;106:190–194.
Andrews LG, Markert ML. Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency. J Biol Chem 1992;267:7834–7838.
Puck JM. IL2RG base: a database of gamma c-chain defects causing human X-SCID. Immunol Today 1996;17:507–511.
Pepper AE, Buckley RH, Small TN, Puck JM. Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency. Am J Hum Genet 1995;57:564–571.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, C., Zhang, ZY., Wu, JF. et al. Clinical characteristics and mutation analysis of X-linked severe combined immunodeficiency in China. World J Pediatr 9, 42–47 (2013). https://doi.org/10.1007/s12519-011-0330-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12519-011-0330-4