SA Pathology at the Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Ann Neurol. 2010 Apr;67(4):542-6. doi: 10.1002/ana.21909.
The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were approximately 35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy.
常见癫痫的遗传结构在很大程度上尚不清楚。HCN 通道是极好的癫痫候选基因，因为它们具有基本的神经生理作用。在热性惊厥和热性惊厥附加症的患者中进行筛查，发现 2.4%的人携带 HCN2 中的常见三联脯氨酸缺失（delPPP），而在血库对照中仅为 0.2%。突变 HCN2 通道产生的电流比对照大约大 35%；这是使用自动化电生理学和适当的样本量揭示的一种效应。这是 HCN2 与家族性癫痫的首次关联，证明 HCN2 电流的功能获得是多基因癫痫的潜在原因。
