Finding commonality in autism and congenital heart disease Free

Autism spectrum disorder (ASD) and congenital heart disease (CHD) frequently occur together, but the molecular mechanisms underlying this comorbidity are unclear. As CHD is typically identified before birth, understanding which CHD variants are autism associated could help predict the risk of developing autism. Here, Helen Willsey and colleagues study a group of ciliary genes that are associated with autism and CHD. Gene variants associated with autism typically affect neural progenitor cell proliferation. To investigate which CHD variants also disrupt neural progenitor cells, the researchers conduct a multiplexed CRISPR interference proliferation and survival screen in human induced pluripotent stem cell (iPSC)-derived neural progenitor cells. They identify a cluster of genes associated with both ASD and CHD that impacts ciliary biology. Cilia are hair-like protrusions on the cell surface involved in processes from signalling to fluid flow generation. In vitro perturbation of seven genes in the cluster impairs primary cilia formation. Of the seven genes, the researchers focus on taok1, an ASD gene predicted to be associated with CHD. In vivo depletion of taok1 in frogs leads to defects in motile cilia formation and heart development. Together, the findings reveal that cilia biology is involved in the increased likelihood of autism in people with CHD.