Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome
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ORIGINAL ARTICLE
Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome Xiaoming Bai1 • Jing Liu1 • Zhiyong Zhang2 • Chaohong Liu1 • Yongjie Zhang1 Wenjing Tang1 • Rongxin Dai1 • Junfeng Wu2 • Xuemei Tang2 • Yu Zhang2 • Yuan Ding2 • Liping Jiang1 • Xiaodong Zhao1,2,3
•
Ó Springer Science+Business Media New York 2015
Abstract Mutations in Recombination Activating Genes (RAG1 and RAG2) are common genetic causes of severe combined immunodeficiency (SCID) and Omenn syndrome (OS). The clinical, immunologic, and genetic characteristics of RAG mutations in Chinese patients with SCID or OS have not been studied in detail. In this research, 22 RAG mutations were identified in 15 Chinese patients, including 10 novel mutations in RAG1 (R108X, M630T, E510X, S666P, E669K, C730Y, A857V, K847E, L922PfsX7, and L1025FfsX39) and 4 in RAG2 (R73C, I427GfsX12, P432L, and 311insL). L1025FfsX39 is a potential RAG1 hot-spot mutation in the Chinese population. The distribution of RAG1 mutations rather than mutation type seemed to differ between SCID and OS patients. The thymic output of T lymphocytes, TCR
Xiaoming Bai and Jing Liu have contributed equally to this work.
Electronic supplementary material The online version of this article (doi:10.1007/s12026-015-8723-4) contains supplementary material, which is available to authorized users. & Xiaodong Zhao [email protected] 1
Research Center for Immunologic and Infectious Diseases, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
2
Division of Immunology, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
3
Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children’s Hospital of Chongqing Medical University, Chongqing 400014, China
rearrangement, and T cell proliferation were severely impaired in RAG mutant patients. These findings will contribute to the early diagnosis and treatment of SCID and OS to a certain extent. Keywords Omenn syndrome Recombination Activating Gene 1 Recombination Activating Gene 2 Severe combined immunodeficiency Mutation
Introduction Severe combined immunodeficiency (SCID) comprises a heterogeneous group of inherited immunologic disorders with profound defects in cellular and humoral immunity, characterized by fatal opportunistic infections [1]. Without appropriate reconstitution of the immune system, patients usually die within the first 2 years of life [1, 2]. Mutations in Recombination Activating Gene 1 and 2 (RAG1, OMIM no. 179615; RAG2, OMIM no. 179616) are common genetic causes of SCID. RAG recombinases play crucial roles in variable (V), diversity (D), and joining (J) gene segment recombination of immunoglobulin and T cell receptor (TCR) genes and in lymphoid cell differentiation early in development [3–5]. RAG mutations were initially identified as ca
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