Synaptic transmission. Over the last several years, pathogenic variants in multiple genes involved in synaptic transmission have been identified in early-onset epilepsies. STXBP1 and STX1B both encode components of the SNARE complex, a complicated protein complex that mediates the fusion of the plasma membrane of the presynapse and the synaptic vesicle to allow for neurotransmitter release. DNM1, encoding the dynamin-1 protein, plays an essential role in recycling synaptic vesicles back into the presynapse after neurotransmitter release. A new study by Myers and collaborators has identified several patients with de novo variants in PPP3CA, which encodes another protein involved in synaptic vesicle recycling, further highlighting the importance of synaptic transmission in the etiology of severe neurodevelopmental disorders. In the interest of full disclosure, I am also a co-author on this study. Continue reading →