西亚试剂：Protein Interactome Reveals Converging Molecular Pathways A

Protein Interactome Reveals Converging Molecular Pathways Among Autism Disorders

Sakai, Yasunari; Shaw, Chad A.; Dawson, Brian C.; Dugas, Diana V.; Al-Mohtaseb, Zaina; Hill, David E.; Zoghbi, Huda Y.

To uncover shared pathogenic mechanisms among the highly heterogeneous autism spectrum disorders (ASDs), we developed a proteininteraction network that identified hundreds of new interactions among proteins encoded by ASD-associated genes. We discoveredunexpectedly high connectivity between SHANK and TSC1, previously implicated in syndromic autism, suggesting that common molecularpathways underlie autistic in distinct syndromes. ASD patients were more likely to harbor copy number variationsthat encompass network genes than were control subjects. We also identified, in patients with idiopathic ASD, three de novolesions (deletions in 16q23.3 and 15q22 and one duplication in Xq28) that involve three network genes (NECAB2, PKM2, and FLNA). The protein interaction network thus provides a framework for identifying causes of idiopathic autism and for understandingmolecular pathways that underpin both syndromic and idiopathic ASDs.