Yamakawa Kazuhiro, Meisler Miriam H., Isom Lori L.
The genes , , and encode the voltage-gated sodium channel (VGSC) α-subunits Nav1.1, Nav1.2, and Nav1.6, respectively. Dravet syndrome is eat the severe end of the disease spectrum caused by variants, and Nav1.1 haploinsufficiency in parvalbumin-positive inhibitory neurons has been proposed as a primary cause for the disease. Nav1.2 is predominantly expressed in excitatory neurons in neocortex and hippocampus. is the gene with the largest number of de novo variants in patients with autism spectrum disorder and/or intellectual disability, and those are mainly truncations. variants also appear in patients with epileptic encephalopathies, but those are mostly missense. Variants of have been reported in a number of patients with variable epilepsies. Gain-of-function missense variants are the most common in developmental and epileptic encephalopathy associated with motor manifestations such as ataxia and choreoathetosis in the most severe cases. encodes the non-pore-forming VGSCβ1 and β1B subunits, which are multifunctional channel regulatory molecules expressed in excitatory and inhibitory neurons. variants are reported in patients with epilepsies of multiple etiologies. In vitro and animal model studies have provided critical insights into pathological mechanisms of the diseases caused by genetic variation in these genes.
基因 、 和 分别编码电压门控钠通道（VGSC）α亚基Nav1.1、Nav1.2和Nav1.6。德雷维特综合征处于由 变异引起的疾病谱的严重一端，有人提出小白蛋白阳性抑制性神经元中的Nav1.1单倍体不足是该疾病的主要原因。Nav1.2主要在新皮层和海马体的兴奋性神经元中表达。 是自闭症谱系障碍和/或智力残疾患者中从头变异数量最多的基因，且这些变异主要是截短变异。 变异也出现在癫痫性脑病患者中，但大多是错义变异。在许多患有不同癫痫的患者中都报告了 变异。功能获得性错义变异在与运动表现相关的发育性和癫痫性脑病中最为常见，在最严重的情况下表现为共济失调和舞蹈手足徐动症。 编码非孔形成性VGSCβ1和β1B亚基，它们是在兴奋性和抑制性神经元中表达的多功能通道调节分子。在多种病因的癫痫患者中报告了 变异。体外和动物模型研究为这些基因的遗传变异所引起疾病的病理机制提供了关键见解。
