title: DE NOVO MUTATIONS IN AUTISM IMPLICATE THE SYNAPTIC ELIMINATION NETWORK.
abstract: Autism has been shown to have a major genetic risk component; the architecture of documented autism in families has been over and again shown to be passed down for generations. While inherited risk plays an important role in the autistic nature of children, de novo (germline) mutations have also been implicated in autism risk. Here we find that autism de novo variants verified and published in the literature are Bonferroni-significantly enriched in a gene set implicated in synaptic elimination. Additionally, several of the genes in this synaptic elimination set that were enriched in protein-protein interactions (CACNA1C, SHANK2, SYNGAP1, NLGN3, NRXN1, and PTEN) have been previously confirmed as genes that confer risk for the disorder. The results demonstrate that autism-associated de novos are linked to proper synaptic pruning and density, hinting at the etiology of autism and suggesting pathophysiology for downstream correction and treatment.
authors.affiliation: Department of Bioengineering, Stanford University, 318 Campus Drive Stanford, CA 94305, USA, guhan@stanford.edu.
authors.forename: Guhan Ram
authors.initials: GR
authors.lastname: Venkataraman
authors.forename: Chloe
authors.initials: C
authors.lastname: O'Connell
authors.forename: Fumiko
authors.initials: F
authors.lastname: Egawa
authors.forename: Dorna
authors.initials: D
authors.lastname: Kashef-Haghighi
authors.forename: Dennis P
authors.initials: DP
authors.lastname: Wall
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D054351:Electrical Synapses / Q000235:genetics / Q000473:pathology; D005260:Female; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008957:Models, Genetic; D008959:Models, Neurological