SCGN deficiency is a risk factor for autism spectrum disorder

We identify secretagogin (SCGN), a regulator of synaptic transmission, as a new risk factor for ASD. Two heterozygous loss-of-function mutations in SCGN are presented in ASD probands. Deletion of Scgn in zebrafish or mice leads to autism-like behaviors. Mechanistically, Scgn deficiency leads to reduced oxytocin signaling and inflammatory activation in animal models as well as ASD probands. Importantly, we demonstrate that administration of oxytocin and anti-inflammatory drugs can attenuate ASD-associated defects caused by SCGN deficiency. Altogether, we identify a convergence between a potential autism genetic risk factor SCGN and the pathological deregulation in oxytocinergic signaling and immune responses, providing potential treatment for ASD patients suffering from SCGN deficiency.