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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp <t>electrophysiology</t> ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.
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Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp electrophysiology ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.

Journal: bioRxiv

Article Title: Excitatory Dysfunction and Phenotypic Rescue in a Human Neuronal Model of SCN2A -Related Disorders

doi: 10.64898/2026.05.18.725745

Figure Lengend Snippet: Overview of Analysis of p.M1879T patient-derived Neurons A. Left , EEG showing tonic seizure of the patient heterozygous for the p.M1879T missense variant ( right ) in SCN2A . B. Schematic of iPSC creation, CRSPR/Cas9 editing, and neuron differentiation using dual SMAD/Wnt pathway inhibition combined with NGN2 overexpression. C. Timeline of neuron culture and differentiation/maturation process for path-clamp electrophysiology ( top ) and all-optical ‘Optopatch’ electrophysiology ( bottom ), with experimental DIV timepoints shown below.

Article Snippet: For all-optical electrophysiology experiments, a nearly identical protocol was used except for EdU (5-ethynyl-2’-deoxyuridine, Thermo Fisher Scientific) treatment in place of AraC.

Techniques: Derivative Assay, Variant Assay, Inhibition, Over Expression