A New IL-2RG Gene Mutation in an X-linked SCID Identified through TREC/KREC Screening: a Case Report
Abstract
Severe combined immunodeficiency (SCID) represents a rare group of primary immunodeficiency disorders (PIDs), with known or unknown genetic alterations. Here, we report a new interleukin 2 receptor, gamma chain (IL-2RG) mutation in an Iranian SCID newborn.The patient was a 6-day old boy with a family history of PID. The child was screened using a molecular-based analysis for the assessment of T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). Moreover, a complete immunological evaluation and gene sequencing was performed.Results showed undetectable TREC but a high level of KREC copy numbers. Flow cytometric data indicated low numbers of T and NK cells, but elevated number of B cells. A novel substitution in IL2RG: c.675 C>A, leading to p.225 Ser>Arg was found. Based on the functional analysis, the mutation is predicted to be damaging. The patient was diagnosed as a T B+ NK X-linked SCID.
1. 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; (125 Suppl 2):88-95.
2. Baker MW, Grossman WJ, Laessig RH, Hoffman GL, Brokopp CD, Kurtycz DF, et al. Development of a routine newborn screening protocol for severe combined immunodeficiency. J Allergy Clin Immunol 2009;124(3):522-7.
3. Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, et al. Statewide newborn screening for severe T-cell lymphopenia. JAMA 2009;302(22):2465-70.
4. Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S, Hammarstrom L, et al. Primary immunodeficiency mutation databases. Adv Genet 2001;43:103-88.
5. Amado MC. Primary immunodeficiency update and newborn screening. Mo Med 2011; 108(5):350-3.
6. Puck JM. Population-based newborn screening for severe combined immunodeficiency: steps toward implementation. J Allergy Clin Immunol 2007;120(4):760-8.
7. Adeli MM, Buckley RH. Why newborn screening for severe combined immunodeficiency is essential: a case report. Pediatrics 2010; 126(2):e465-9.
8. Borte S, Wang N, Oskarsdottir S, von Dobeln U, Hammarstrom L. Newborn screening for primary immunodeficiencies: beyond SCID and XLA. Ann N Y Acad Sci 2011; 1246:118-30.
9. Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol 2005;115(2):391-8.
10. Puck JM. The case for newborn screening for severe combined immunodeficiency and related disorders. Ann N Y Acad Sci 2011; 1246:108-17.
11. Lev A, Simon AJ, Trakhtenbrot L, Goldstein I, Nagar M,Stepensky P, et al. Characterizing T cells in SCID patients presenting with reactive or residual T lymphocytes. Clin Dev Immunol 2012; 2012:261470.
12. Gerstel-Thompson JL, Wilkey JF, Baptiste JC, Navas JS, Pai SY, Pass KA, et al. High-throughput multiplexed T- cell-receptor excision circle quantitative PCR assay with internal controls for detection of severe combined immunodeficiency in population-based newborn screening. Clin Chem 2010; 56(9):1466-74.
13. Borte S, von Dobeln U, Fasth A, Wang N, Janzi M, Winiarski J, et al. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood 2012; 119(11):2552-5.
14. Borte S, von Dobeln U, Hammarstrom L. Guidelines for newborn screening of primary immunodeficiency diseases. Curr Opin Hematol 2013; 20(1):48-54.
15. Saadat M, Ansari-Lari M, Farhud DD. Consanguineous marriage in Iran. Ann Hum Biol 2004; 31(2):263-9.
16. Yeganeh M, Heidarzade M, Pourpak Z, Parvaneh N, Rezaei N, Gharagozlou M, et al. Severe combined immunodeficiency: a cohort of 40 patients. Pediatr Allergy Immunol 2008; 19(4):303-6.
17. Schmalstieg FC, Goldman AS. Immune consequences of mutations in the human common gamma-chain gene. Mol Genet Metab 2002; 76(3):163-71.
18. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, et al. Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73: 147-157. 1993. J Immunol 2008; 181(9):5817-27.
19. Kalman L, Lindegren ML, Kobrynski L, Vogt R, Hannon H, Howard JT, 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. Genet Med 2004;6(1):16-26.
20. Kwan A, Church JA, Cowan MJ, Agarwal R, Kapoor N, Kohn DB, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years. J Allergy Clin Immunol 2013;132(1):140-50.
21. Puck JM. Neonatal screening for severe combined immune deficiency. Curr Opin Allergy Clin Immunol 2007; 7(6):522-7.
22. Rezaei N, Pourpak Z, Aghamohammadi A, Farhoudi A, Movahedi M, Gharagozlou M, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry. Am J Reprod Immunol 2006; 56(2):145-51.
23. The Harriet Lane handbook: a manual for pediatric house officers Custer, Jason W; Rau, Rachel E; Johns Hopkins Hospital Children's Medical and Surgical Center. 18th ed. Philadelphia, PA: Mosby/Elsevier, c2009. NLM ID:101318759.
| Files | ||
| Issue | Vol 14, No 4 (2015) | |
| Section | Case Report(s) | |
| Keywords | ||
| Interleukin-2 Receptor gamma Chain Severe Combined Immune Deficiency T-cell receptor excision circles kappa-deleting recombination excision circles | ||
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