Molecular and immunological characterization of DNA ligase IV deficiency
Molecular and immunological characterization of DNA ligase IV deficiency
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DNA 连接酶 IV 缺陷的分子和免疫学特征
DOI：
10.1016/j.clim.2015.12.016
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发表时间：
2016-02-01
影响因子：
8.6
通讯作者：
Zhao, Xiaodong
中科院分区：
文献类型：
--
作者：
Jiang, Jinqiu;Tang, Wenjing;Zhao, Xiaodong
DNA 连接酶 IV (LIG4) 缺陷是一种极其罕见的常染色体隐性遗传原发性免疫缺陷病，由 LIG4 突变引起。迄今为止，全球报告的患者病例不到 30 例。此前尚未在 LIG4 中发现回复突变。这项研究招募了 7 名患有 LIG4 缺乏症的中国患者，他们患有联合免疫缺陷、小头畸形和生长迟缓。一名患者（P1）患上非霍奇金淋巴瘤。 4 名患者的 T 细胞增殖功能受损，T 细胞受体多样性出现偏差。在中国人群中发现了 LIG4 的 5 个新突变和一个潜在的热点突变 (c.833G > T; p.R278L)。对 P6 中的 T 细胞、NK 细胞、粒细胞和口腔粘膜细胞进行 TA 克隆分析，发现野生型克隆和包含母本和父本遗传突变的克隆，表明可能存在体细胞逆转，需要进一步研究，因为无法对所有死亡患者进行功能或蛋白质测定，也没有可用的细胞系。 (C) 2016 Elsevier Inc. 保留所有权利。
DNA ligase IV (LIG4) deficiency is an extremely rare autosomal recessive primary immunodeficiency disease caused by the LIG4 mutation. To date, fewer than 30 cases of patients have been reported worldwide. No reversion mutations have been previously identified in LIG4. This study enrolled seven Chinese patients with LIG4 deficiency who presented with combined immunodeficiency, microcephaly, and growth retardation. One patient (P1) acquired non-Hodgkin lymphoma. Four patients had impaired T cell proliferation function and skewed T cell receptor diversity. Five novel mutations in LIG4 and a potential hotspot mutation (c.833G > T; p.R278L) in the Chinese population were identified. TA cloning analysis of T cells, NK cells, granulocytes, and oral mucosa cells in P6 revealed wild-type clones and clones that contained both maternally and paternally inherited mutations, indicating possible somatic reversion which need further investigation since no functional or protein assays were possible for all the patients died and no cell lines were available. (C) 2016 Elsevier Inc. All rights reserved.