New research shows that variants of SYNGAP1, a gene previously thought only to affect synapses between mature neurons, may disrupt early development in the brain’s cortex, a region involved in higher-order cognitive functions in humans.

By Cristy Lytal

Two sculptures representing a human neuron and a radial glia cell, inspired by the findings published by the Quadrato Lab in Nature Neuroscience.
Credit: Sculptures by Jane Kwak; photo by Sergio Bianco

The gene SYNGAP1, the variants of which are top risk factors for Autism Spectrum Disorder (ASD), has previously unappreciated effects on the developing brain, according to a new study published in Nature Neuroscience. The study shows how disease-causing variants of SYNGAP1, thought primarily to affect synapses between mature neurons, could disrupt early development in a key region of the brain known as the cortex.

“Our findings reframe our understanding of the developmental role not only of SYNGAP1, but also of an entire category of ASD risk genes previously thought to be primarily involved in the function of synapses, which are the interfaces that allow nerve cells to communicate with each other,” said corresponding author Giorgia Quadrato, an assistant professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC. “Ultimately, this points to the importance of pursuing ASD therapies that target not only synapse function, but also early developmental defects.”

Disease-causing variants of SYNGAP1, a gene that provides instructions for making a protein that plays a critical role in the synapses, are associated with a variety of clinical manifestations. At least half of patients with a variant of the gene have been formally diagnosed with autistic features, and the majority of patients also experience intellectual disability, developmental delay, and epilepsy. (…Read More)