A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial seizures in infancy

被引：79

作者：

Ishii, Atsushi ^{[1
]}

Shioda, Mutsuki ^{[2
]}

Okumura, Akihisa ^{[3
]}

Kidokoro, Hiroyuki ^{[4
]}

Sakauchi, Masako ^{[2
]}

Shimada, Shino ^{[2
,5
]}

Shimizu, Toshiald ^{[3
]}

Osawa, Makiko ^{[2
]}

Hirose, Shinichi ^{[1
]}

Yamamoto, Toshiyuki ^{[5
]}

机构：

[1] Fukuoka Univ, Sch Med, Dept Pediat, Jonan Ku, Fukuoka 8140180, Japan

[2] Tokyo Womens Med Univ, Dept Pediat, Shinjuku Ku, Tokyo 1628666, Japan

[3] Juntendo Univ, Fac Med, Dept Pediat, Bunkyo Ku, Tokyo 1138421, Japan

[4] Nagoya Univ, Grad Sch Med, Dept Pediat, Showa Ku, Nagoya, Aichi 4668550, Japan

[5] Womens Med Univ, Inst Integrated Med Sci, Shinjuku Ku, Tokyo 1628666, Japan

来源：

GENE | 2013年 / 531卷 / 02期

基金：

日本学术振兴会;

关键词：

KCNT1; Malignant migrating partial seizures in infancy; Molecular operating environment; Hot spot; Vagus nerve stimulation; Clorazepate; CHANNEL; EPILEPSY; STIRIPENTOL; CHILDREN; VOLTAGE;

D O I：

10.1016/j.gene.2013.08.096

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

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收藏

页码：467 / 471

页数：5

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