Calame Daniel G, Herman Isabella, Riviello James J
Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, TX 77030, United States.
Epilepsy Behav Rep. 2021 Jan 7;15:100425. doi: 10.1016/j.ebr.2020.100425. eCollection 2021.
encodes a neuronal synaptic vesicle glycoprotein essential for neurotransmitter release. Altered SV2A function leads to epilepsy in animal models, yet only two reports of human variants have linked to syndromic drug-resistant epileptic encephalopathies and epilepsy. SV2A is also the binding site for the commonly used antiseizure medication levetiracetam (LEV). However, information about how rare variants influence LEV response is lacking. Here, we report a two-year-old child with new-onset epilepsy found to have a heterozygous rare variant in (NM_014849.5:c.1978G>A;p.Gly660Arg) who developed refractory status epilepticus after escalation of LEV treatment for initial baseline seizure control. This report provides additional evidence that monoallelic pathogenic variants cause epilepsy and that genetic variation in could lead to paradoxical seizure worsening when treated with LEV.
编码一种对神经递质释放至关重要的神经元突触小泡糖蛋白。在动物模型中，SV2A功能改变会导致癫痫，但仅有两篇关于人类变体的报告将其与综合征性耐药性癫痫性脑病及癫痫联系起来。SV2A也是常用抗癫痫药物左乙拉西坦（LEV）的结合位点。然而，关于罕见变体如何影响LEV反应的信息尚缺。在此，我们报告一名两岁新发癫痫患儿，其在（NM_014849.5:c.1978G>A;p.Gly660Arg）中发现有杂合罕见变体，在为控制初始基线发作而加大LEV治疗剂量后发展为难治性癫痫持续状态。本报告提供了额外证据，证明单等位基因致病变体可导致癫痫，且SV2A的基因变异在用LEV治疗时可能导致矛盾的癫痫恶化。
