Department of Pediatrics, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Gene. 2013 Dec 1;531(2):467-71. doi: 10.1016/j.gene.2013.08.096. Epub 2013 Sep 10.
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.
我们对两名患有婴儿恶性游走性部分性癫痫的非相关患者进行了 KCNT1 分析。这两名患者从两个月大开始就出现难治性局灶性癫痫。他们的癫痫发作具有单一发作中癫痫灶转移的特征，对大多数抗癫痫药物均有抵抗，但对迷走神经刺激在一名患者中有效，氯硝西泮在另一名患者中有效。通过标准的 Sanger 测序方法对 KCNT1 进行双向测序。在 KCNT1 通道的孔区鉴定出两个患者中存在从头发生的 c.862G>A（p.Gly288Ser）错义突变，而之前报道的所有 KCNT1 突变主要发生在细胞内 C 末端区域。计算分析表明 Gly288Ser 突变可能导致分子结构和离子通道特性的改变。由于 G 到 A 的转换位于 CG 二核苷酸序列，如之前报道的 KCNT1 突变，因此从头发生的 KCNT1 突变的反复出现表明这些位置是热点。
