A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in infancy (SMEI) inherited from a father with febrile seizures
A missense mutation in SCN1A in brothers with severe myoclonic epilepsy in infancy (SMEI) inherited from a father with febrile seizures
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DOI：
10.1016/j.braindev.2004.11.005
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发表时间：
2005-09-01
影响因子：
1.7
通讯作者：
Segawa, M
中科院分区：
文献类型：
--
作者：
Kimura, K;Sugawara, T;Segawa, M
婴儿期严重肌阵挛性癫痫（Severe myoclonic epilepsy in infant，SMEI）是一种发生于1岁以内的年龄依赖性癫痫性脑病，是难治性癫痫之一。在SMEI患者中经常发现电压门控钠通道a亚单位1型基因（SCN 1A）的杂合突变;这些突变中的三分之二是截短突变（无义和移码），三分之一是错义突变。虽然大多数报告的SMEI病例都是作为散发性突变出现的，但SMEI患者的近亲也显示出比一般人群更高的其他类型癫痫发生率。在这里，我们报告了一个家族性的情况下，SMEI，其中两个兄弟受到SMEI，而他们的父亲以前经历过简单的热性惊厥。一项基于基因的分析在两个兄弟和他们的父亲的SCNI A基因（c.5138G > A，S1713 N）中发现了一种新的错义突变。临床上，两个兄弟姐妹表现出运动失败，婴儿后期后睡眠-觉醒周期受损，以及随后出现的额叶病灶。在这两个兄弟的临床表现的相似性表明，脑干的元素，特别是胺能神经元的损害，在婴儿后期后，在SMEI的发展。然而，兄弟姐妹不同的SMEI和肌阵挛发作的年龄，以及在言语延迟的严重程度。我们的分子和临床研究结果表明，不同的遗传背景和/或环境因素可能会严重影响SCN 1A突变患者的临床特征，与这种疾病中普遍存在的异质性一致。(c)2004 Elsevier B. V.保留所有权利。
Severe myoclonic epilepsy in infancy (SMEI) is an age-dependent epileptic encephalopathy occurring in the first year of life and is one of the intractable epilepsies. Heterozygous mutations in the voltage-gated sodium channel a subunit type 1 gene (SCN1A) are frequently identified in patients with SMEI; two-thirds of these mutations are truncation mutations (non-sense and frameshift), and one-third are missense mutations. Although most reported SMEI cases arise as sporadic mutations, close relatives of SMEI patients have also been shown to manifest other types of epilepsies at a higher rate than that in the general population. Here, we report a familial case of SMEI, in which two brothers were affected with SMEI while their father had previously experienced simple febrile seizures. A gene-based analysis identified a novel missense mutation in the SCNI A gene (c.5138G > A, S1713N) in both brothers and in their father. Clinically, both siblings showed failure in locomotion, an impairment of the sleep-wake cycle after late infancy, and the subsequent appearance of frontal foci. The similarity in clinical manifestations in both brothers suggests that the impairment of elements of the brainstem, particularly aminergic neurons, develops after late infancy in SMEI However, the siblings differed in age at onset of SMEI and of myoclonic seizures, as well as in the severity of speech delay. Our molecular and clinical findings suggest that different genetic backgrounds and/or environmental factors may critically affect the clinical features of patients with SCN1A mutations, consistent with the heterogeneity prevalent in this disorder. (c) 2004 Elsevier B.V. All rights reserved.