title: Protein interactome reveals converging molecular pathways among autism disorders.
abstract: To uncover shared pathogenic mechanisms among the highly heterogeneous autism spectrum disorders (ASDs), we developed a protein interaction network that identified hundreds of new interactions among proteins encoded by ASD-associated genes. We discovered unexpectedly high connectivity between SHANK and TSC1, previously implicated in syndromic autism, suggesting that common molecular pathways underlie autistic phenotypes in distinct syndromes. ASD patients were more likely to harbor copy number variations that encompass network genes than were control subjects. We also identified, in patients with idiopathic ASD, three de novo lesions (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 understanding molecular pathways that underpin both syndromic and idiopathic ASDs.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Human Genetics, Baylor College of Medicine, and Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Sakai
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Brian C
authors.initials: BC
authors.lastname: Dawson
authors.forename: Diana V
authors.initials: DV
authors.lastname: Dugas
authors.forename: Zaina
authors.initials: Z
authors.lastname: Al-Mohtaseb
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D002659:Child Development Disorders, Pervasive / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007231:Infant, Newborn; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods; D020798:Two-Hybrid System Techniques
chemical_list: D009419:Nerve Tissue Proteins