biostudies-literatureQue ZHHS | National Institutes of HealthFulbright-Colciencias scholarshipPurdue Big Idea Challenge 2.0 on AutismFamilieSCN2A foundationNCATS NIH HHSNIEHS NIH HHSNIAID NIH HHSIndiana Clinical and Translational Sciences InstituteNINDS NIH HHSNCI NIH HHSNational Science Foundation (NSF) Graduate Research Fellowship ProgramRalph W. and Grace M. Showalter Research Trust Fund10194-10208https://www.ebi.ac.uk/biostudies/studies/S-EPMC8660047biostudies-literatureUnknown41(49)With the wide adoption of genomic sequencing in children having seizures, an increasing number of <i>SCN2A</i> genetic variants have been revealed as genetic causes of epilepsy. Voltage-gated sodium channel Nav1.2, encoded by gene <i>SCN2A</i>, is predominantly expressed in the pyramidal excitatory neurons and supports action potential (AP) firing. One recurrent <i>SCN2A</i> genetic variant is L1342P, which was identified in multiple patients with epileptic encephalopathy and intractable seizures. However, the mechanism underlying L1342P-mediated seizures and the pharmacogenetics of this variant in human neurons remain unknown. To understand the core phenotypes of the L1342P variant in human neurons, we took advantage of a reference human-induced pluripotent stem cell (hiPSC) line from a mThe Journal of neuroscience : the official journal of the Society for NeuroscienceHyperexcitability and Pharmacological Responsiveness of Cortical Neurons Derived from Human iPSCs Carrying Epilepsy-Associated Sodium Channel Nav1.2-L1342P Genetic Variant.PMC8660047R01 NS117585R01 AI150847R03 NS108229Action Potential GrantDGE-1842166R01 CA212403R01 ES031401R01 NS123154UL1 TR002529Wu JSkarnes WCShafer JMZhang JBowman ABTrader DJWettschurack KSchaber JATukker AMXiao TEaton MYuan CYang YHuang ZQue ZOlivero-Acosta MIXie JHu CDYunis LChen XRochet JCfalseHyperexcitability and Pharmacological Responsiveness of Cortical Neurons Derived from Human iPSCs Carrying Epilepsy-Associated Sodium Channel Nav1.2-L1342P Genetic Variant.With the wide adoption of genomic sequencing in children having seizures, an increasing number of <i>SCN2A</i> genetic variants have been revealed as genetic causes of epilepsy. Voltage-gated sodium channel Nav1.2, encoded by gene <i>SCN2A</i>, is predominantly expressed in the pyramidal excitatory neurons and supports action potential (AP) firing. One recurrent <i>SCN2A</i> genetic variant is L1342P, which was identified in multiple patients with epileptic encephalopathy and intractable seizures. However, the mechanism underlying L1342P-mediated seizures and the pharmacogenetics of this variant in human neurons remain unknown. To understand the core phenotypes of the L1342P variant in human neurons, we took advantage of a reference human-induced pluripotent stem cell (hiPSC) line from a m2021-01-01T00:00:00Z2021 Dec2025-04-22T05:52:20.795Z2025-04-05T21:27:47.101ZS-EPMC86600473471623110.1523/JNEUROSCI.0564-21.202110.1523/jneurosci.0564-21.2021