Differential Functional Changes of Nav1.2 Channel Causing SCN2A-Related Epilepsy and Status Epilepticus During Slow Sleep.
Differential Functional Changes of Nav1.2 Channel Causing SCN2A-Related Epilepsy and Status Epilepticus During Slow Sleep.
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Nav1.2 通道的差异功能变化导致 SCN2A 相关癫痫和慢速睡眠期间癫痫持续状态
DOI：
10.3389/fneur.2021.653517
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发表时间：
2021
影响因子：
3.4
通讯作者：
Feng J
中科院分区：
文献类型：
--
作者：
Miao P;Tang S;Ye J;Tang J;Wang J;Zheng C;Li Y;Feng J
背景资料：由SCN 2A基因编码的Nav1.2是脑表达的电压门控钠通道，已知与神经发育障碍相关，从良性家族性新生儿婴儿癫痫发作（BFIS）到发育和癫痫性脑病（DEE）和自闭症谱系障碍。有趣的是，在SCN 2A相关癫痫中发现了缓慢睡眠期间的癫痫持续状态（ESES），其加重了认知障碍。然而，SCN2A的功能特点及其与ESES的关系尚未见报道。方法：我们在此通过转染HEK293T细胞的全细胞膜片钳研究，研究了未发表的从头V911A和其他两种已发表的变体在SCN 2A相关疾病和ESES患者中的功能后果。结果：在DEE患者中检测到的未发表的V911A和已发表的K1933M变体表现出深刻的功能获得性（GOF）变化。另一种已发表的BFIS变体S863F作为功能丧失（LOF）变化显著降低了电流密度。V911A患者的难治性癫痫从3个月大起通过使用奥卡西平（OXC）的精确治疗得到控制。ESES是在18个月时发现的，在无牙颌期。我们最终选择了甲基强的松龙联合左乙拉西坦和硝西泮的积极治疗来消除ESES，而不是OXC的精确治疗。结论：在DEE和BFIS表型中，SCN2A基因GOF和LOF变异均可导致ESES。对SCN 2A相关性癫痫患者应定期进行脑电图监测，即使在无癫痫发作期也应定期进行脑电图监测。
Background: Nav1.2 encoded by the SCN2A gene is a brain-expressed voltage-gated sodium channel known to be associated with neurodevelopment disorders ranging from benign familial neonatal infantile seizures (BFIS) to developmental and epileptic encephalopathy (DEE) and autism spectrum disorder. Interestingly, status epilepticus during slow sleep (ESES), which aggravates cognitive impairment, has been found in SCN2A-related epilepsy. However, the functional features and the relationship between SCN2A and ESES have not been researched. Method: We herein investigated the functional consequences of an unpublished de novo V911A and the other two published variants in patients with SCN2A-related disorder and ESES by whole-cell patch-clamp studies in transfected HEK293T cells. Results: The unpublished V911A and published K1933M variants detected in patients with DEE exhibited a profound gain-of-functional (GOF) change. Another published BFIS variant S863F significantly reduced current density as a loss-of-functional (LOF) change. The refractory epilepsy in the patient with V911A was controlled by using the precise treatment of oxcarbazepine (OXC) since the age of 3 months. ESES was found at 18 months during the seizure-free period. We finally chose an aggressive treatment for eliminating ESES by using methylprednisolone combined with levetiracetam and nitrazepam instead of the precise treatment of OXC. Conclusion: Both GOF and LOF variants in the SCN2A gene can lead to ESES among the phenotypes of DEE and BFIS. We should monitor the electroencephalogram regularly in the patients with SCN2A-related epilepsy even during their seizure-free period.
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影响因子：
30.8
作者：
Carvill, Gemma L.;Regan, Brigid M.;Yendle, Simone C.;O'Roak, Brian J.;Lozovaya, Natalia;Bruneau, Nadine;Burnashev, Nail;Khan, Adiba;Cook, Joseph;Geraghty, Eileen;Sadleir, Lynette G.;Turner, Samantha J.;Tsai, Meng-Han;Webster, Richard;Ouvrier, Robert;Damiano, John A.;Berkovic, Samuel F.;Shendure, Jay;Hildebrand, Michael S.;Szepetowski, Pierre;Scheffer, Ingrid E.;Mefford, Heather C.
通讯作者：
Mefford, Heather C.
影响因子：
2.9
作者：
Kessi M;Peng J;Yang L;Xiong J;Duan H;Pang N;Yin F
通讯作者：
Yin F
影响因子：
4.7
作者：
Bonardi, Claudia M.;Mignot, Cyril;Rubboli, Guido
通讯作者：
Rubboli, Guido
影响因子：
29
作者：
de Kovel, Carolien G. F.;Syrbe, Steffen;Koeleman, Bobby P. C.
通讯作者：
Koeleman, Bobby P. C.
影响因子：
5.6
作者：
Seegmueller, Caroline;Deonna, Thierry;Roulet-Perez, Eliane
通讯作者：
Roulet-Perez, Eliane