Disruption of the autism-associated gene alters synaptic development and neuronal signaling in patient iPSC-glutamatergic neurons.

is an autism spectrum disorder (ASD) risk gene and encodes a voltage-gated sodium channel. However, the impact of ASD-associated SCN2A variants on human neuron development is unknown. We studied SCN2A using isogenic induced pluripotent stem cells (iPSCs), and patient-derived iPSCs harboring a R607* truncating variant.

Neuron-specific protein network mapping of autism risk genes identifies shared biological mechanisms and disease-relevant pathologies.

There are hundreds of risk genes associated with autism spectrum disorder (ASD), but signaling networks at the protein level remain unexplored. We use neuron-specific proximity-labeling proteomics (BioID2) to identify protein-protein interaction (PPI) networks for 41 ASD risk genes. Neuron-specific PPI networks, including synaptic transmission proteins, are disrupted by de novo missense variants.