A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy
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- 作者：Atsushi Ishii ; Mutsuki Shioda ; Akihisa Okumura ; Hiroyuki Kidokoro ; Masako Sakauchi ; Shino Shimada ; Toshiaki Shimizu ; Makiko Osawa ; Shinichi Hirose ; Toshiyuki Yamamoto
- 关键词：MMPSI ; malignant migrating partial seizures in infancy ; ADNFLE ; autosomal dominant nocturnal frontal lobe epilepsy ; CLZ ; clorazepate ; MOE ; molecular operating environment
- 刊名：Gene
- 出版年：2013
- 出版时间：1 December, 2013
- 年：2013
- 卷：531
- 期：2
- 页码：467-471
- 全文大小：1269 K
文摘
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.