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

Research output: Contribution to journalArticle

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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

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Severe Combined Immunodeficiency
T-cells
T-Lymphocytes
Mutation
Genes
Cells
Mosaicism
B-Lymphocytes
V(D)J Recombination
Reading Frames
Eosinophilia
Missense Mutation
Genetic Recombination
Proteins
Phenotype

ASJC Scopus subject areas

  • Hematology

Cite this

Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency. / Wada, Taizo; Toma, Tomoko; Okamoto, Hiroyuki; Kasahara, Yoshihito; Koizumi, Shoichi; Agematsu, Kazunaga; Kimura, Hirokazu; Shimada, Akira; Hayashi, Yasuhide; Kato, Masahiko; Yachie, Akihiro.

In: Blood, Vol. 106, No. 6, 15.09.2005, p. 2099-2101.

Research output: Contribution to journalArticle

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, vol. 106, no. 6, pp. 2099-2101. https://doi.org/10.1182/blood-2005-03-0936
Wada, Taizo ; Toma, Tomoko ; Okamoto, Hiroyuki ; Kasahara, Yoshihito ; Koizumi, Shoichi ; Agematsu, Kazunaga ; Kimura, Hirokazu ; Shimada, Akira ; Hayashi, Yasuhide ; Kato, Masahiko ; Yachie, Akihiro. / Oligoclonal expansion of T lymphocytes with multiple second-site mutations leads to Omenn syndrome in a patient with RAG1-deficient severe combined immunodeficiency. In: Blood. 2005 ; Vol. 106, No. 6. pp. 2099-2101.
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AU - Koizumi, Shoichi

AU - Agematsu, Kazunaga

AU - Kimura, Hirokazu

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AU - Kato, Masahiko

AU - Yachie, Akihiro

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AB - 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.

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