GIGYF1-disturbed IGF-1R recycling: a potential contributor to autism spectrum disorder pathogenesis?

Abstract

Autism spectrum disorder (ASD) is a highly variable and heritable neurodevelopmental disease (NDD) with strong genetic underpinnings. In this issue of the JCI, Chen et al. analyzed 2 previously reported, large-scale sequenced ASD cohorts and reported that GIGYF1 is the second most mutated among ASD risk genes. In this issue of the JCI, Chen et al. used a conditional mouse model combined with molecular technologies based on human genetic analyses to determine the critical role of GIGYF1 in ASD. GIGYF1-deficiency affected the recycling of IGF-1R, thereby suppressing the IGF-1R/ERK signaling pathway. Disruption of GIGYF1 in the developing mouse brain led to social deficits and cognitive impairments. These findings extend our understanding of ASD pathogenesis and provide an avenue for developing potentially effective preventions and treatments for patients with ASD.