A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy
A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy
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DOI：
10.1016/j.gene.2013.08.096
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发表时间：
2013-12-01
期刊：
影响因子：
3.5
通讯作者：
Yamamoto, Toshiyuki
中科院分区：
文献类型：
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作者：
Ishii, Atsushi;Shioda, Mutsuki;Yamamoto, Toshiyuki
我们对两名患有婴儿期恶性迁移性部分性癫痫发作的无关患者进行了 KCNT1 分析。两名患者从两个月大起就出现顽固性局灶性癫痫发作。他们的癫痫发作特点是单次癫痫发作期间癫痫病灶发生转移，并且对大多数抗癫痫药物有耐药性，但其中一种药物对迷走神经刺激有反应，另一种药物对氯氮平有反应。通过标准桑格测序方法分析 KCNT1 的双向测序。在两名患者的 KCNT1 通道孔区域均发现了从头 c.862G>A (p.Gly288Ser) 错义突变，而之前报告中的所有 KCNT1 突变主要在细胞内 C 端区域发现。计算分析表明 Gly288Ser 突变可能导致分子结构和离子通道特性发生变化。由于 G 到 A 的转变位于 CG 二核苷酸序列（如之前报道的 KCNT1 突变），因此 KCNT1 新生突变的反复出现表明了这些位置的热点。 (C) 2013 Elsevier B.V. 保留所有权利。
We performed analysis of KCNT1 in two unrelated patients with malignant migrating partial seizures in infancy. Both patients had intractable focal seizures since two months of age. Their seizures were characterized by a shift of epileptic focus during a single seizure and were resistant to most antiepileptic drugs but responded to vagus nerve stimulation in one and clorazepate in the other. Bidirectional sequencing for KCNT1 was analyzed by standard Sanger sequencing method. A de novo c.862G>A (p.Gly288Ser) missense mutation was identified at the pore region of KCNT1 channel in both patients, whereas all KCNT1 mutations in the previous reports were identified mostly in the intracellular C-terminal region. Computational analysis suggested possible changes in the molecular structure and the ion channel property induced by the Gly288Ser mutation. Because the G-to-A transition was located at CG dinucleotide sequences as previously reported for KCNT1 mutations, the recurrent occurrence of de novo KCNT1 mutations indicated the hot spots of these locations. (C) 2013 Elsevier B.V. All rights reserved.