1] Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur, India [2] Department of Biochemistry, G.R.Medical College, Gwalior, India.
J Hum Genet. 2013 Sep;58(9):573-80. doi: 10.1038/jhg.2013.77. Epub 2013 Jul 25.
The voltage-gated sodium channels are fundamental units that evoke the action potential in excitable cells such as neurons. These channels are integral membrane proteins typically consisting of one α-subunit, which forms the larger central pore of the channel, and two smaller auxiliary β-subunits, which modulate the channel functions. Genetic alterations in the SCN1A gene coding for the α-subunit of the neuronal voltage-gated sodium ion channel, type 1 (NaV 1.1), is associated with a spectrum of seizure-related disorders in human, ranging from a relatively milder form of febrile seizures to a more severe epileptic condition known as the Dravet syndrome. Among the epilepsy genes, the SCN1A gene perhaps known to have the largest number of disease-associated alleles. Here we present a meta-analysis on the SCN1A gene variants and provide comprehensive information on epilepsy-associated gene variants, their frequency, the predicted effect on the protein, the ethnicity of the affected along with the inheritance pattern and the associated epileptic phenotype. We also summarize our current understanding on the pathophysiology of the SCN1A gene defects, disease mechanism, genetic modifiers and their clinical and diagnostic relevance.
电压门控钠离子通道是在神经元等可兴奋细胞中引发动作电位的基本单位。这些通道是完整的膜蛋白，通常由一个α亚基组成，该亚基形成通道的较大中央孔，还有两个较小的辅助β亚基，调节通道功能。编码神经元电压门控钠离子通道 1 型（NaV1.1）的α亚基的 SCN1A 基因突变与人类一系列与癫痫发作相关的疾病有关，从相对较轻的热性惊厥到更严重的癫痫疾病称为 Dravet 综合征。在癫痫基因中，SCN1A 基因可能具有最多与疾病相关的等位基因。在这里，我们对 SCN1A 基因变异进行了荟萃分析，并提供了有关癫痫相关基因变异、其频率、对蛋白质的预测影响、受影响人群的种族以及遗传模式和相关癫痫表型的综合信息。我们还总结了我们对 SCN1A 基因突变的病理生理学、疾病机制、遗传修饰因子及其临床和诊断相关性的现有认识。
