De Novo SCN8A Mutation Identified by Whole-Exome Sequencing in a Boy With Neonatal Epileptic Encephalopathy, Multiple Congenital Anomalies, and Movement Disorders
De Novo SCN8A Mutation Identified by Whole-Exome Sequencing in a Boy With Neonatal Epileptic Encephalopathy, Multiple Congenital Anomalies, and Movement Disorders
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DOI：
10.1177/0883073813511300
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发表时间：
2014-12-01
影响因子：
1.9
通讯作者：
Talvik, Tiina
中科院分区：
文献类型：
--
作者：
Vaher, Ulvi;Noukas, Margit;Talvik, Tiina
癫痫性脑病是一组临床和遗传上异质性的疾病，其中大多数病因不明。我们使用亲子三人组的全外显子组测序来确定一名患有新生儿癫痫、运动障碍和多种先天性异常的男孩早期婴儿癫痫性脑病的原因，该男孩在 17 个月大时因呼吸系统疾病死亡，并在 SCN8A（电压门控钠通道 VIII 型 α）中发现了从头杂合错义突变 (c.3979A>G；p.Ile1327Val)亚基）基因。通过桑格测序在先证者中证实了该变异。由于与 SCN8A 突变相关的临床表型之前仅在少数患有或不患有癫痫发作的患者中被发现，因此这些数据与我们的结果一起表明 SCN8A 突变可导致具有广泛表型谱的早期婴儿癫痫性脑病。值得进行更多研究来确定 SCN8A 突变的患病率以及对癫痫性脑病的影响。
Epileptic encephalopathies represent a clinically and genetically heterogeneous group of disorders, majority of which are of unknown etiology. We used whole-exome sequencing of a parent-offspring trio to identify the cause of early infantile epileptic encephalopathy in a boy with neonatal seizures, movement disorders, and multiple congenital anomalies who died at the age of 17 months because of respiratory illness and identified a de novo heterozygous missense mutation (c.3979A>G; p.Ile1327Val) in SCN8A (voltage-gated sodium-channel type VIII alpha subunit) gene. The variant was confirmed in the proband with Sanger sequencing. Because the clinical phenotype associated with SCN8A mutations has previously been identified only in a few patients with or without epileptic seizures, these data together with our results suggest that mutations in SCN8A can lead to early infantile epileptic encephalopathy with a broad phenotypic spectrum. Additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies.