Variants in SCN1A

Mutations in the SCN1A gene, which codes for an important ion channel in the brain (the voltage-gated sodium channel), are an important cause of epilepsy. These mutations can cause a range of disorders, ranging from fairly treatable epilepsies to syndromes with severe and disabling seizures, such as Dravet syndrome. 

At least some of the variability in how different patients are affected by mutations in this gene might be caused by different effects of the mutations at the molecular level. Some mutations may make the channels open abnormally often, whilst others may make them not work at all. 

In this research stream, we combine recording what goes on in individual channels under different conditions, with computer models of neurons. We are also developing novel patient-specific animal models of individual mutations. This work may improve our ability to predict the effect of mutations for individual patients in the future.

Collaborators

Kathleen Gorman
Paediatric Neurologist
Children's University Hospital, Temple Street
Dublin (IRE)

Elaine Hughes
Consultant Paediatric Neurologist
King's Health Partners
London (UK)

Mary King
Professor of Paediatrics
University College Dublin
Dublin (IRE)

Colin Peters
Postdoctoral Researcher
Simon Fraser University, 
Burnaby (CA)

Peter Ruben
Professor of Biomedical Physiology and Kinesiology
Simon Fraser University, 
Burnaby (CA)


SCN1A channel structure

Characterising the effects of individual mutations can yields insights about how an SCN1A mutations can lead to epilepsy. 

Peters et al. 2016 Sci Rep 10.1038/srep31879

Screen Shot 2018-04-22 at 20.04.00.png

This code implements the patch-clamp recordings made above in a Hodgkin-Huxley model to simulate its effects on neuronal function.

Github: SCN1A Hodgkin Huxley Model