15例中国重症联合免疫缺陷病和奥门综合征患者RAG突变的临床、免疫学及遗传学特征
Clinical, immunologic, and genetic characteristics of RAG mutations in 15 Chinese patients with SCID and Omenn syndrome.
作者信息
Bai Xiaoming, Liu Jing, Zhang Zhiyong, Liu Chaohong, Zhang Yongjie, Tang Wenjing, Dai Rongxin, Wu Junfeng, Tang Xuemei, Zhang Yu, Ding Yuan, Jiang Liping, Zhao Xiaodong
机构信息
Research Center for Immunologic and Infectious Diseases, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Division of Immunology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
出版信息
Immunol Res. 2016 Apr;64(2):497-507. doi: 10.1007/s12026-015-8723-4.
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 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.
重组激活基因（RAG1和RAG2）突变是严重联合免疫缺陷（SCID）和奥门综合征（OS）常见的遗传病因。中国SCID或OS患者中RAG突变的临床、免疫学及遗传学特征尚未得到详细研究。本研究在15例中国患者中鉴定出22种RAG突变，其中包括RAG1的10种新突变（R108X、M630T、E510X、S666P、E669K、C730Y、A857V、K847E、L922PfsX7和L1025FfsX39）以及RAG2的4种新突变（R73C、I427GfsX12、P432L和311insL）。L1025FfsX39是中国人群中潜在的RAG1热点突变。SCID和OS患者中RAG1突变的分布而非突变类型似乎有所不同。RAG突变患者的T淋巴细胞胸腺输出、TCR重排及T细胞增殖均严重受损。这些发现将在一定程度上有助于SCID和OS的早期诊断及治疗。
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