title: Epigenetic factors and autism spectrum disorders.
abstract: Autism is a complex neurodevelopmental disorder that has significant phenotypic overlap with several diseases, many of which fall within the broader category of autism spectrum disorders (ASDs). The etiology of the disorder is unclear and seems to involve a complex interplay of polygenic as well as environmental factors. We discuss evidence that suggests that epigenetic dysregulation is highly implicated as a contributing cause of ASDs and autism. Specifically, we examine neurodevelopmental disorders that share significant phenotypic overlap with ASDs and feature the dysregulation of epigenetically modified genes including UBE3A, GABA receptor genes, and RELN. We then look at the dysregulated expression of implicated epigenetic modifiers, namely MeCP2, that yield complex and varied downstream pleiotropic effects. Finally, we examine epigenetically mediated parent-of-origin effects through which paternal gene expression dominates that of maternal contributing to contrasting phenotypes implicated in ASDs. Such preliminary evidence suggests that elucidating the complex role of epigenetic regulations involved in ASDs could prove vital in furthering our understanding of the complex etiology of autism and ASDs.
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, Georgetown University School of Medicine, 3900 Reservoir Rd. NW, Washington, DC 20057, USA.
authors.forename: Bess M
authors.initials: BM
authors.lastname: Flashner
authors.forename: Mark E
authors.initials: ME
authors.lastname: Russo
authors.forename: Jenine E
authors.initials: JE
authors.lastname: Boileau
authors.forename: Derek W
authors.initials: DW
authors.lastname: Leong
authors.forename: G Ian
authors.initials: GI
authors.lastname: Gallicano
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis / Q000235:genetics; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000628:therapy; D019175:DNA Methylation / Q000187:drug effects; D044127:Epigenesis, Genetic; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018740:Genetic Heterogeneity; D018392:Genomic Imprinting / Q000235:genetics; D005838:Genotype; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D010641:Phenotype; D011218:Prader-Willi Syndrome / Q000235:genetics; D018079:Receptors, GABA / Q000096:biosynthesis / Q000235:genetics; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D014424:Turner Syndrome / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D056572:Histone Deacetylase Inhibitors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D018079:Receptors, GABA; D000091042:Reelin Protein; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; C000717127:RELN protein, human; D012697:Serine Endopeptidases