A blueprint for research on Shankopathies: a view from research on autism spectrum disorder

Abstract

Autism spectrum disorders (ASD) are associated with mutations in a host of genes including a number that function in synaptic transmission. Phelan McDermid syndrome involves mutations in SHANK3 which encodes a protein that forms a scaffold for glutamate receptors at the synapse. SHANK3 is one of the genes that underpins the synaptic hypothesis for ASD. We discuss this hypothesis with a view to the broader context of ASD and with special emphasis on highly penetrant genetic disorders including Shankopathies. We propose a blueprint for near and longer-term goals for fundamental and translational research on Shankopathies.

Keywords: Shank3; autism; neurodevelopmental disorders; synaptic genes.