Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan.
Clin Immunol. 2011 Feb;138(2):172-7. doi: 10.1016/j.clim.2010.11.005. Epub 2010 Dec 4.
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.
重组激活基因（RAG1 或 RAG2）突变可导致多种免疫缺陷。本文报道了 5 个家系的 5 例 RAG 缺陷病例：3 例为 Omenn 综合征，1 例为严重联合免疫缺陷，1 例为伴有寡克隆 TCRγδ（+）T 细胞、自身免疫和巨细胞病毒感染的联合免疫缺陷。遗传缺陷具有异质性，包括 6 种新的 RAG 突变。除 RAG2 中的 Met443Ile 外，所有错义突变均位于 RAG1 或 RAG2 的活性核心区域。每个突变体的 V(D)J 重组活性各不相同，从野生型活性的一半到无活性不等，但在每个患者中均证明平均重组活性显著降低。RAG2 中的 Met443Ile 重组活性降低可能表明 RAG2 的非核心区域在 V(D)J 重组中具有重要作用。这些发现表明，功能评估与分子分析相结合有助于我们更全面地了解 RAG 缺陷。
