Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.
Mutations in XRCC4 cause primordial dwarfism without causing immunodeficiency.
复制标题
XRCC4 突变会导致原始侏儒症，但不会引起免疫缺陷。
DOI：
10.1038/jhg.2016.46
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Adachi N.
中科院分区：
文献类型：
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作者：
Saito S;Kurosawa A;Adachi N.
在2014年至2015年的连续报道中，X射线修复交叉互补蛋白4（XRCC4）被确定为原始侏儒症的新致病基因。XRCC4对于非同源末端连接（NHEJ）是不可或缺的，NHEJ是修复DNA双链断裂的主要途径。由于NHEJ是淋巴细胞发育过程中V（D）J重组所必需的，因此通常认为XRCC4的异常会导致严重的联合免疫缺陷。然而，与预期相反，在携带XRCC4突变的原始侏儒症患者中没有观察到明显的免疫缺陷。在这里，我们描述了导致疾病的各种XRCC4突变，并讨论了它们对NHEJ和V（D）J重组的影响。
In successive reports from 2014 to 2015, X-ray repair cross-complementing protein 4 (XRCC4) has been identified as a novel causative gene of primordial dwarfism. XRCC4 is indispensable for non-homologous end joining (NHEJ), the major pathway for repairing DNA double-strand breaks. As NHEJ is essential for V (D) J recombination during lymphocyte development, it is generally believed that abnormalities in XRCC4 cause severe combined immunodeficiency. Contrary to expectations, however, no overt immunodeficiency has been observed in patients with primordial dwarfism harboring XRCC4 mutations. Here, we describe the various XRCC4 mutations that lead to disease and discuss their impact on NHEJ and V (D) J recombination.