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Cis-Attenuation of Pathogenic Scn8a Variant Causing Childhood Epilepsy Reveals Opposing Transcriptional Programs Driving NaV1.6 Gain and Loss of Function Phenotypes
The findings show that the two clinical directions of SCN8A disease have distinct tissue-level correlates and call for opposite therapeutic logic, channel or injury-cascade suppression for GoF and restoration of channel output for LoF, and identify a conserved, seizure-driven injury core as a tractable cross-disease ta...