Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency

Taizo Wada, Tomoko Toma, Hiroyuki Okamoto, Yoshihito Kasahara, Shoichi Koizumi, Kazunaga Agematsu, Hirokazu Kimura, Akira Shimada, Yasuhide Hayashi, Masahiko Kato, Akihiro Yachie

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68 Citations (Scopus)

Abstract

Omenn syndrome (OS) is a rare primary immunodeficiency characterized by the presence of activated/oligoclonal T cells, eosinophilia, and the absence of circulating B cells. OS patients carry leaky mutations of recombination activating genes (RAG1 or RAG2) resulting in partial V(D)J recombination activity, whereas null mutations cause severe combined immunodeficiency with absence of mature T and B cells (T-B- SCID). Here we describe somatic mosaicism due to multiple second-site mutations in a patient with RAG1 deficiency. We found that he is homozygous for a single base deletion in the RAG1 gene, which results in frameshift and likely abrogates the protein function. However, the patient showed typical OS features. Molecular analysis revealed that several second-site mutations, all of which restored the RAG1 reading frame and resulted in missense mutations, were demonstrated in his T cells. These findings suggest that his revertant T-cell mosaicism is responsible for OS phenotype switched from T-B- SCID.

Original languageEnglish
Pages (from-to)2099-2101
Number of pages3
JournalBlood
Volume106
Issue number6
DOIs
Publication statusPublished - Sep 15 2005
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Wada, T., Toma, T., Okamoto, H., Kasahara, Y., Koizumi, S., Agematsu, K., Kimura, H., Shimada, A., Hayashi, Y., Kato, M., & Yachie, A. (2005). Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency. Blood, 106(6), 2099-2101. https://doi.org/10.1182/blood-2005-03-0936