DNA ligase IV syndrome; a review.
DNA ligase IV syndrome; a review.
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DOI：
10.1186/s13023-016-0520-1
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发表时间：
2016-10-07
影响因子：
3.7
通讯作者：
Gennery AR
中科院分区：
文献类型：
--
作者：
Altmann T;Gennery AR
DNA 连接酶 IV 缺陷是一种罕见的原发性免疫缺陷，LIG4 综合征，通常与其他全身特征相关。 DNA 连接酶 IV 是非同源末端连接机制的一部分，需要修复 DNA 双链断裂。它广泛表达，需要防止突变和细胞凋亡，突变和细胞凋亡可能是由细胞内事件（例如 DNA 复制和减数分裂）或细胞外事件（包括活性氧和电离辐射损伤）引起的 DNA 双链断裂引起的。在发育中的淋巴细胞中，需要 DNA 连接酶 IV 来修复淋巴细胞受体发育过程中诱导的编程性 DNA 双链断裂。 LIG4 亚等位性突变的患者表现出一系列表型，从正常到严重的联合免疫缺陷。然而，所有这些都表现出对电离辐射的敏感性。常见的相关特征包括原始生长障碍、严重小头畸形、一系列学习困难、骨髓发育不全和易患淋巴恶性肿瘤。诊断研究包括免疫表型分析和放射敏感性测试。一些患者以小头畸形为主要特征，但免疫力似乎正常。治疗主要是支持性的，尽管在少数病例中也使用了造血干细胞移植。
DNA ligase IV deficiency is a rare primary immunodeficiency, LIG4 syndrome, often associated with other systemic features. DNA ligase IV is part of the non-homologous end joining mechanism, required to repair DNA double stranded breaks. Ubiquitously expressed, it is required to prevent mutagenesis and apoptosis, which can result from DNA double strand breakage caused by intracellular events such as DNA replication and meiosis or extracellular events including damage by reactive oxygen species and ionising radiation. Within developing lymphocytes, DNA ligase IV is required to repair programmed DNA double stranded breaks induced during lymphocyte receptor development. Patients with hypomorphic mutations in LIG4 present with a range of phenotypes, from normal to severe combined immunodeficiency. All, however, manifest sensitivity to ionising radiation. Commonly associated features include primordial growth failure with severe microcephaly and a spectrum of learning difficulties, marrow hypoplasia and a predisposition to lymphoid malignancy. Diagnostic investigations include immunophenotyping, and testing for radiosensitivity. Some patients present with microcephaly as a predominant feature, but seemingly normal immunity. Treatment is mainly supportive, although haematopoietic stem cell transplantation has been used in a few cases.
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影响因子：
3.5
作者：
Evans, PM;Woodbine, L;Jeggo, PA
通讯作者：
Jeggo, PA
影响因子：
3.9
作者：
Murray, Jennie E.;Bicknell, Louise S.;Yigit, Goekhan;Duker, Angela L.;van Kogelenberg, Margriet;Haghayegh, Sara;Wieczorek, Dagmar;Kayserili, Huelya;Albert, Michael H.;Wise, Carol A.;Brandon, January;Kleefstra, Tjitske;Warris, Adilia;van der Flier, Michiel;Bamforth, J. Steven;Doonanco, Kurston;Ades, Lesley;Ma, Alan;Field, Michael;Johnson, Diana;Shackley, Fiona;Firth, Helen;Woods, C. Geoffrey;Nuernberg, Peter;Gatti, Richard A.;Hurles, Matthew;Bober, Michael B.;Wollnik, Bernd;Jackson, Andrew P.
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Jackson, Andrew P.
影响因子：
14.2
作者：
Cowan, Morton J.;Gennery, Andrew R.
通讯作者：
Gennery, Andrew R.
影响因子：
2
作者：
Ben-Omran, TI;Cerosaletti, K;Nezarati, MM
通讯作者：
Nezarati, MM
影响因子：
7.4
作者：
Miller-Pinsler, Lutfiya;Pinto, Daniel J.;Wells, Peter G.
通讯作者：
Wells, Peter G.