International Journal of Hematology

, Volume 80, Issue 4, pp 332–335 | Cite as

Characterization of a Novel Nonsense Mutation in the Interleukin-7 Receptor α Gene in a Korean Patient with Severe Combined Immunodeficiency

  • Eun-Kyeong Jo
  • Hoon Kook
  • Toru Uchiyama
  • Ikuko Hakozaki
  • Young-Ok Kim
  • Chang-Hwa Song
  • Jeong-Kyu Park
  • Hirokazu Kanegane
  • Shigeru Tsuchiya
  • Satoru Kumaki
Article

Abstract

Although it has been suggested that defective interleukin 7 receptor (IL-7R) signaling is one of the principal causes of severe combined immunodeficiency disease (SCID) in mice and humans, little is known about the molecular and clinical characteristics of human IL-7Rα mutations. We report a novel mutation of the IL-7Rα gene in a Korean SCID patient with a greatly diminished T-cell count but normal numbers of B-cells and natural killer (NK) cells. Using direct sequencing and restriction fragment length polymorphism analysis, we identified a C →T nucleotide change at position 638. This change resulted in a nonsense mutation (R206stop) in this patient. Both parents were heterozygous for C/T at this site. The results of this study emphasize the importance of characterization of IL-7Rα mutations in SCID patients with diminished T-cell numbers but normal numbers of B-cells and NK cells.

Key words

Severe combined immunodeficiency IL-7 receptor a chain Mutation Korean 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fischer A. Severe combined immunodeficiencies (SCID). Clin Exp Immunol. 2000;122:143–149.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Primary immunodeficiency diseases: report of an IUIS Scientific Committee. International Union of Immunological Societies. Clin Exp Immunol. 1999:118(suppl 1):1–28.Google Scholar
  3. 3.
    Buckley RH, Schiff SE, Schiff RI, et al. Hematopoietic stem cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999:340:508–516.CrossRefGoogle Scholar
  4. 4.
    Takeshita T, Asao H, Ohtani K, et al. Cloning of the -γ chain of the human IL-2 receptor. Science. 1992:257:379–382.CrossRefPubMedGoogle Scholar
  5. 5.
    Noguchi M, Yi H, Rosenblatt HM, et al. Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell. 1993:73:147–157.CrossRefPubMedGoogle Scholar
  6. 6.
    Puck JM, Deschenes SM, Porter JC, et al. The interleukin-2 receptor γ chain maps to Xq13.1 and is mutated in X-linked severe combined immunodeficiency, SCIDX1. Hum Mol Genet. 1993: 2:1099–1104.CrossRefPubMedGoogle Scholar
  7. 7.
    Sugamura K, Asao H, Kondo M, et al. The interleukin-2 receptor γ chain: its role in the multiple cytokine receptor complexes and T cell development in XSCID. Annu Rev Immunol. 1996: 14:179–205.CrossRefPubMedGoogle Scholar
  8. 8.
    Macchi P, Villa A, Gillani S, et al. Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature. 1995:377:65–68.CrossRefPubMedGoogle Scholar
  9. 9.
    Russell SM, Tayebi N, Nakajima H, et al. Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development. Science. 1995:270:797–800.CrossRefPubMedGoogle Scholar
  10. 10.
    Schwarz K, Gauss GH, Ludwig L, et al. RAG mutations in human B cell-negative SCID. Science. 1996:274:97–99.CrossRefPubMedGoogle Scholar
  11. 11.
    Moshous D, Callebaut I, de Chasseval R, et al. Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell. 2001: 105:177–186.CrossRefPubMedGoogle Scholar
  12. 12.
    Kung C, Pingel JT, Heikinheimo M, et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med. 2000:6:343–345.CrossRefPubMedGoogle Scholar
  13. 13.
    Orlic D, Girard LJ, Lee D, Anderson SM, Puck JM, Bodine DM. Interleukin-7Rα mRNA expression increases as stem cells differentiate into T and B lymphocyte progenitors. Exp Hematol. 1997: 25:217–222.PubMedGoogle Scholar
  14. 14.
    Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet. 1998:20:394–397.CrossRefPubMedGoogle Scholar
  15. 15.
    Roifman CM, Zhang J, Chitayat D, Sharfe N. A partial deficiency of interleukin-7Rα is sufficient to abrogate T-cell development and cause severe combined immunodeficiency. Blood. 2000: 96:2803–2807.PubMedGoogle Scholar
  16. 16.
    Kumaki S, Villa A, Asada H, et al. Identification of anti-herpes simplex virus (HSV) antibody-producing B cells in a patient with an atypical RAG1 immunodeficiency. Blood. 2001: 98:1464–1468.CrossRefPubMedGoogle Scholar
  17. 17.
    Kumaki S, Ishii N, Minegishi M, et al. Functional role of IL-4 and IL-7 in the development of X-linked severe combined immunodeficiency. Blood. 1999;93:607–612.PubMedGoogle Scholar
  18. 18.
    Kennedy MK, Glaccum M, Brown SN, et al. Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med. 2000;191:771–780.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lodolce JP, Boone DL, Chai S, et al. IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity. 1998;9:669–676.CrossRefPubMedGoogle Scholar
  20. 20.
    Ozaki K, Spolski R, Feng CG, et al. A critical role for IL-21 in regulating immunoglobulin production. Science. 2002:298:1630–1634.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2004

Authors and Affiliations

  • Eun-Kyeong Jo
    • 1
  • Hoon Kook
    • 2
  • Toru Uchiyama
    • 4
  • Ikuko Hakozaki
    • 4
  • Young-Ok Kim
    • 2
  • Chang-Hwa Song
    • 1
  • Jeong-Kyu Park
    • 1
  • Hirokazu Kanegane
    • 3
  • Shigeru Tsuchiya
    • 4
  • Satoru Kumaki
    • 4
  1. 1.Department of Microbiology, College of MedicineChungnam National UniversityDaejeon
  2. 2.Department of PediatricsChonnam National University Medical SchoolKwangjuKorea
  3. 3.Department of Pediatrics, Faculty of MedicineToyama Medical and Pharmaceutical UniversityToyama
  4. 4.Department of Pediatric Oncology, Institute of Development, Aging and CancerTohoku UniversityAoba-Ku, SendaiJapan

Personalised recommendations