期刊
DNA REPAIR
卷 10, 期 3, 页码 314-321出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2010.12.002
关键词
Nijmegen breakage syndrome (NBS); Ataxia-telangiectasia-like disorder (ATLD); Nijmegen breakage syndrome-like disorder (NBSLD); ATM; MRE11; NBS1; Microcephaly
资金
- Ministry of Education, Culture, Sports, Science and Technology
- Grants-in-Aid for Scientific Research [23650626, 23300363, 23710068, 22710056] Funding Source: KAKEN
MRE11 and NBS1 function together as components of a MRE11/RAD5O/NBS1 protein complex, however deficiency of either protein does not result in the same clinical features. Mutations in the NBN gene underlie Nijmegen breakage syndrome (NBS), a chromosomal instability syndrome characterized by microcephaly, bird-like faces, growth and mental retardation, and cellular radiosensitivity. Additionally, mutations in the MRE1 1A gene are known to lead to an ataxia-telangiectasia-like disorder (ATLD), a late-onset, slowly progressive variant of ataxia-telangiectasia without microcephaly. Here we describe two unrelated patients with NBS-like severe microcephaly (head circumference -10.2 SD and -12.8 SD) and mutations in the MRE1 1A gene. Both patients were compound heterozygotes for a truncating or missense mutation and carried a translationally silent mutation. The truncating and missense mutations were assumed to be functionally debilitating. The translationally silent mutation common to both patients had an effect on splicing efficiency resulting in reduced but normal MRE11 protein. Their levels of radiation-induced activation of ATM were higher than those in ATLD cells. (C) 2010 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据