Mutation screening of AP3M2 in Japanese epilepsy patients
Mutation screening of AP3M2 in Japanese epilepsy patients
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DOI：
10.1016/j.braindev.2006.12.004
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发表时间：
2007-09-01
影响因子：
1.7
通讯作者：
Kojima, Toshio
中科院分区：
文献类型：
--
作者：
Huang, Ming-Chih;Okada, Motohiro;Kojima, Toshio
有证据表明，某些类型的癫痫表现出强烈的遗传易感性，这一点已经得到了很好的记录。AP3M2基因被认为是致痫基因，因为AP3M2基因敲除的小鼠表现出自发性癫痫发作的症状。为了探讨AP3M2基因是否导致癫痫的易感性，我们对6种癫痫类型的190例患者的基因组DNA进行了突变筛查，筛查涉及AP3M2的全部9个外显子及其相应的外显子-内含子边界。虽然没有检测到错义和无义突变，但我们鉴定了21个序列变异，其中16个变异是新的。在21个变异中，I I位于5‘和3’非编码区，其余变异位于内含子。尽管目前的研究未能确定可能导致癫痫的AP3M2突变，但我们的结果表明，一些AP3M2突变仍然是未映射疾病的候选基因，包括癫痫、热性癫痫和其他与GABA能传递功能异常相关的神经元发育障碍。(C)2007 Elsevier B.V.保留所有权利。
Evidence that some types of epilepsies show strong genetic predisposition has been well documented. AP3M2 is considered to be an epileptogenic gene because AP3M2 knockout mice exhibit symptoms of spontaneous epileptic seizures. In order to investigate whether the AP3M2 gene causes susceptibility to epilepsy, we performed mutation screening of the genomic DNA of 190 patients with six epilepsy types; this screening involved all the 9 exons and the relevant exon-intron boundaries of AP3M2. Although neither missense nor nonsense mutations were detected, we identified 21 sequence variations, of which 16 variations were novel. Of the 21 variations, I I were detected in 5' and 3' UTRs, while the remaining variations were detected in introns. Although the present study failed to identify the possible AP3M2 mutations that may cause epilepsy, our results suggest that some AP3M2 mutations still remain candidates for unmapped disorders including epilepsy, febrile seizure, and other neuronal developmental disorders associated with functional abnormalities of GABAergic transmission. (c) 2007 Elsevier B.V. All rights reserved.