Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams Syndrome
Contribution of CYLN2 and GTF2IRD1 to neurological and cognitive symptoms in Williams Syndrome
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DOI：
10.1016/j.nbd.2006.12.009
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发表时间：
2007-04-01
影响因子：
6.1
通讯作者：
De Zeeuw, C. I.
中科院分区：
文献类型：
--
作者：
van Hagen, J. M.;van der Geest, J. N.;De Zeeuw, C. I.
威廉姆斯综合征(WS，MIM 194050)是一种由染色体7q11.23上25-30个基因半合子缺失引起的疾病。其中几个基因，包括编码胞浆连接蛋白-115(CYLN2)和通用转录因子(GTF2I和GTF2IRD1)的基因在大脑中表达，可能与WS患者明显的神经和认知功能障碍有关。最近对部分缺失患者的研究表明，GTF2I的半合可能与WS的精神发育迟滞有关。在这里，我们研究了CYLN2和GTF2IRD1是否与WS的运动和认知障碍有关。对一名新患者的行为评估显示，他的认知和运动协调功能明显好于典型的WS患者。对基因特异性的CYLN2和GTF2IRD1基因敲除小鼠的比较分析表明，基因敲除小鼠的胼胝体体积变小，运动协调能力和海马体记忆形成障碍可能归因于CYLN2基因的缺失，而脑室体积的增加可以归因于CYLN2和GTF2IRD1两者。我们的结论是，Williams综合征的运动和认知功能障碍是由多种基因引起的，并且Cyln2杂合缺失是导致这种功能障碍的主要原因之一。(C)2006 Elsevier Inc.保留所有权利。
Williams Syndrome (WS, [MIM 194050]) is a disorder caused by a hemizygous deletion of 25-30 genes on chromosome 7q11.23. Several of these genes including those encoding cytoplasmic linker protein-115 (CYLN2) and general transcription factors (GTF2I and GTF2IRD1) are expressed in the brain and may contribute to the distinct neurological and cognitive deficits in WS patients. Recent studies of patients with partial deletions indicate that hemizygosity of GTF2I probably contributes to mental retardation in WS. Here we investigate whether CYLN2 and GTF2IRD1 contribute to the motoric and cognitive deficits in WS. Behavioral assessment of a new patient in which STX1A and LIMK1, but not CYLN2 and GTF2IRD1, are deleted showed that his cognitive and motor coordination functions were significantly better than in typical WS patients. Comparative analyses of gene specific CYLN2 and GTF2IRD1 knockout mice showed that a reduced size of the corpus callosum as well as deficits in motor coordination and hippocampal memory formation may be attributed to a deletion of CYLN2, while increased ventricle volume can be attributed to both CYLN2 and GTF2IRD1. We conclude that the motor and cognitive deficits in Williams Syndrome are caused by a variety of genes and that heterozygous deletion of CYLN2 is one of the major causes responsible for such dysfunctions. (c) 2006 Elsevier Inc. All rights reserved.