Journal article

A childhood epilepsy mutation reveals a role for developmentally regulated splicing of a sodium channel

Ruwei Xu, Evan A Thomas, Misty Jenkins, Elena V Gazina, Cindy Chiu, Sarah E Heron, John C Mulley, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou

MOLECULAR AND CELLULAR NEUROSCIENCE | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2007

Abstract

Seizure susceptibility is high in human infants compared to adults, presumably because of developmentally regulated changes in neural excitability. Benign familial neonatal-infantile seizures (BFNIS), characterized by both early onset and remission, are caused by mutations in the gene encoding a human sodium channel (NaV1.2). We analyzed neonatal and adult splice forms of NaV1.2 with a BFNIS mutation (L1563V) in human embryonic kidney cells. Computer modeling revealed that neonatal channels are less excitable than adult channels. Introduction of the mutation increased excitability in the neonatal channels to a level similar to adult channels. By contrast, the mutation did not affect the adul..

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