SCN2A severe hypomorphic mutation decreases excitatory synaptic input and causes autism-associated behaviors

Title: SCN2A severe hypomorphic mutation decreases excitatory synaptic input and causes autism-associated behaviors

Affiliation: Cardiovascular Research Institute, Feil Family Brain and Mind Research Institute, Pediatric Neurology, Department of Pediatrics, Weill Cornell Medicine, New York, New York, USA, Weill Cornell Medicine, Center for Autism and the Developing Brain, White Plains, New York, USA, Weill Cornell Autism Research Program, and Sackler Institute for Developmental Psychobiology, Department of Psychiatry, Weill Cornell Medicine, New York, New York, USA

Authors: Hong-Gang Wang, Charlotte C. Bavley, Anfei Li, Rebecca M. Jones, Jonathan Hackett, Yared Bayleyen,1 Francis S. Lee,  Anjali M. Rajadhyaksha, and Geoffrey S. Pitt

Reference: https://insight.jci.org/articles/view/150698

We thank Geoffrey Pitt for providing us with a summary of their work.

Summary:

Background: 

SCN2A encodes a sodium channel that helps neurons send electrical signals. So-called ‘gain-of-function’ mutations make the channel hyperactive and can lead to epilepsy, whereas ‘loss-of-function’ mutations diminish its activity and are typically associated with autism.

What did we find?

This study confirms previous work showing that autism-linked mutations in SCN2A dampen channel activity in neurons. However, the new finding is showing that this genetic change in the sodium channel is linked to clear changes in behavior.

What does this mean?

By showing the direct relationship between genetic changes in sodium channel function and behaviour, it gives us greater confidence that treatments directed towards correcting loss of function in the sodium channel would be expected to reduce autism behaviors. 

How you think this helps future research move forward?

This research helps give a broader understanding of the link between autism and autism-like behviors and sodium channel function. This will help not only those with genetic changes in sodium channel function, such as SCN2A loss of function mutations, but may also help develop treatments for autism spectrum disorder. 

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