Analysis of mutations and recombination activity in RAG-deficient patients

• Asai, Erika

• Wada, Taizo

• Sakakibara, Yasuhisa

• Toga, Akiko

• Toma, Tomoko

• Shimizu, Takashi

• Nampoothiri, Sheela

• Imai, Kohsuke

• Nonoyama, Shigeaki

• Morio, Tomohiro

• Muramatsu, Hideki

• Kamachi, Yoshiro

• Ohara, Osamu

• Yachie, Akihiro

抄録

金沢大学附属病院小児科

Mutations in the recombination activating genes (RAG1 or RAG2) can lead to a variety of immunodeficiencies. Herein, we report 5 cases of RAG deficiency from 5 families: 3 of Omenn syndrome, 1 of severe combined immunodeficiency, and 1 of combined immunodeficiency with oligoclonal TCRγδ+ T cells, autoimmunity and cytomegalovirus infection. The genetic defects were heterogeneous and included 6 novel RAG mutations. All missense mutations except for Met443Ile in RAG2 were located in active core regions of RAG1 or RAG2. V(D)J recombination activity of each mutant was variable, ranging from half of the wild type activity to none, however, a significant decrease in average recombination activity was demonstrated in each patient. The reduced recombination activity of Met443Ile in RAG2 may suggest a crucial role of the non-core region of RAG2 in V(D)J recombination. These findings suggest that functional evaluation together with molecular analysis contributes to our broader understanding of RAG deficiency. © 2010 Elsevier Inc. All rights reserved.

収録刊行物

• Clinical Immunology

  Clinical Immunology 138 (2), 172-177, 2011-02-01

  Elsevier

キーワード

• Omenn syndrome
• RAG deficiency
• SCID
• TCRγδ+ T cells
• V(D)J recombination

詳細情報

• CRID: 1050282810960702720
• NII論文ID: 120002772030
• NII書誌ID: AA11301911
• ISSN: 15216616
• Web Site: http://hdl.handle.net/2297/26269
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
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  • CiNii Articles