Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism
Balanced translocation t(3;18)(p13;q22.3) and points mutation in the ZNF407 gene detected in patients with both moderate non-syndromic intellectual disability and autism
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DOI：
10.1016/j.bbadis.2012.11.009
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发表时间：
2013-03-01
影响因子：
6.2
通讯作者：
Chen, Zheng
中科院分区：
文献类型：
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作者：
Ren, Cong-mian;Liang, Yan;Chen, Zheng
智力残疾是一种常见的疾病。虽然病因仍然不完全清楚，但遗传缺陷是主要原因，包括编码锌指蛋白的基因突变。这些蛋白质通过与DNA结合来调节基因表达。与此一致的知识，我们在这里报告的ID/自闭症患者的ZNF 407基因突变的鉴定。在我们的研究中，一个ID患者与自闭症，相互易位46，XY，t（3;18）（p13;q223）检测。通过使用FISH和长距离PCR方法，我们已经精确地映射了与此易位在3号染色体中的无基因区域和18号染色体中的ZNF 407基因的第三内含子中的断点。后者降低ZNF 407的表达。与这一观察结果相一致，在我们随后对105名具有相似临床表现的ID/自闭症患者的调查中，鉴定出两个错义突变Y 460 C和P1195 A。这些突变导致各个指状结构之间的接头区域中的非保守氨基酸取代。与接头区域对于锌指基序的完整性至关重要一致，两种突变都可能导致ZNF 407功能的丧失。综上所述，我们证明了ZNF 407基因的突变有助于一组自闭症ID患者的发病机制。(C)2012爱思唯尔有限公司版权所有。
Intellectual disability (ID) is a common disease. While the etiology remains incompletely understood, genetic defects are a major contributor, which include mutations in genes encoding zinc finger proteins. These proteins modulate gene expression via binding to DNA. Consistent with this knowledge, we report here the identification of mutations in the ZNF407 gene in ID/autistic patients. In our study of an ID patient with autism, a reciprocal translocation 46,XY,t(3;18)(p13;q223) was detected. By using FISH and long-range PCR approaches, we have precisely mapped the breakpoints associated with this translocation in a gene-free region in chromosome 3 and in the third intron of the ZNF407 gene in chromosome18. The latter reduces ZNF407 expression. Consistent with this observation, in our subsequent investigation of 105 ID/autism patients with similar clinical presentations, two missense mutations Y460C and P1195A were identified. These mutations cause non-conservative amino acid substitutions in the linker regions between individual finger structures. In line with the linker regions being critical for the integrity of zinc finger motifs, both mutations may result in loss of ZNF407 function. Taken together, we demonstrate that mutations in the ZNF407 gene contribute to the pathogenesis of a group of ID patients with autism. (C) 2012 Elsevier B.V. All rights reserved.