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A nonsense mutation in IKBKB causes combined immunodeficiency.

Publication ,  Journal Article
Mousallem, T; Yang, J; Urban, TJ; Wang, H; Adeli, M; Parrott, RE; Roberts, JL; Goldstein, DB; Buckley, RH; Zhong, X-P
Published in: Blood
September 25, 2014

Identification of the molecular etiologies of primary immunodeficiencies has led to important insights into the development and function of the immune system. We report here the cause of combined immunodeficiency in 4 patients from 2 different consanguineous Qatari families with similar clinical and immunologic phenotypes. The patients presented at an early age with fungal, viral, and bacterial infections and hypogammaglobulinemia. Although their B- and T-cell numbers were normal, they had low regulatory T-cell and NK-cell numbers. Moreover, patients' T cells were mostly CD45RA(+)-naive cells and were defective in activation after T-cell receptor stimulation. All patients contained the same homozygous nonsense mutation in IKBKB (R286X), revealed by whole-exome sequencing with undetectable IKKβ and severely decreased NEMO proteins. Mutant IKKβ(R286X) was unable to complex with IKKα/NEMO. Immortalized patient B cells displayed impaired IκBα phosphorylation and NFκB nuclear translocation. These data indicate that mutated IKBKB is the likely cause of immunodeficiency in these 4 patients.

Duke Scholars

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

September 25, 2014

Volume

124

Issue

13

Start / End Page

2046 / 2050

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Severe Combined Immunodeficiency
  • Male
  • Infant
  • Immunology
  • I-kappa B Kinase
  • Humans
  • Homozygote
  • Female
  • Family
 

Citation

APA
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Mousallem, T., Yang, J., Urban, T. J., Wang, H., Adeli, M., Parrott, R. E., … Zhong, X.-P. (2014). A nonsense mutation in IKBKB causes combined immunodeficiency. Blood, 124(13), 2046–2050. https://doi.org/10.1182/blood-2014-04-571265
Mousallem, Talal, Jialong Yang, Thomas J. Urban, Hongxia Wang, Mehdi Adeli, Roberta E. Parrott, Joseph L. Roberts, David B. Goldstein, Rebecca H. Buckley, and Xiao-Ping Zhong. “A nonsense mutation in IKBKB causes combined immunodeficiency.Blood 124, no. 13 (September 25, 2014): 2046–50. https://doi.org/10.1182/blood-2014-04-571265.
Mousallem T, Yang J, Urban TJ, Wang H, Adeli M, Parrott RE, et al. A nonsense mutation in IKBKB causes combined immunodeficiency. Blood. 2014 Sep 25;124(13):2046–50.
Mousallem, Talal, et al. “A nonsense mutation in IKBKB causes combined immunodeficiency.Blood, vol. 124, no. 13, Sept. 2014, pp. 2046–50. Pubmed, doi:10.1182/blood-2014-04-571265.
Mousallem T, Yang J, Urban TJ, Wang H, Adeli M, Parrott RE, Roberts JL, Goldstein DB, Buckley RH, Zhong X-P. A nonsense mutation in IKBKB causes combined immunodeficiency. Blood. 2014 Sep 25;124(13):2046–2050.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

September 25, 2014

Volume

124

Issue

13

Start / End Page

2046 / 2050

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Severe Combined Immunodeficiency
  • Male
  • Infant
  • Immunology
  • I-kappa B Kinase
  • Humans
  • Homozygote
  • Female
  • Family