NeuroMolecular Medicine

, Volume 15, Issue 2, pp 339–350

Epigenetic Factors and Autism Spectrum Disorders

  • Bess M. Flashner
  • Mark E. Russo
  • Jenine E. Boileau
  • Derek W. Leong
  • G. Ian Gallicano
Original Paper

DOI: 10.1007/s12017-013-8222-5

Cite this article as:
Flashner, B.M., Russo, M.E., Boileau, J.E. et al. Neuromol Med (2013) 15: 339. doi:10.1007/s12017-013-8222-5

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.

Keywords

Autism Autism spectrum disorders Epigenetics Neurodevelopmental disorders 

List of Acronyms

3′UTR

3′-Untranslated region

AG

Androgenetic embryo, that is, one having two paternal genome copies

AS

Angelman syndrome

ASDs

Autism spectrum disorders

GABA

Gamma-aminobutyric acid

HMGN1

High mobility group N1 protein

PG

Parthenogenetic, that is, one having two maternal genome copies

PWS

Prader–Willi syndrome

RTT

Rett syndrome

SSADH

Succinic semialdehyde dehydrogenase deficiency

TRD

Transcriptional repression domain

List of Genes and Gene Products

BDNF

Brain-derived neurotrophic factor

DLX5

Encodes a member of a homeobox transcription factor gene family

EGR2

Early growth response protein-2

GABRA5

Gamma-aminobutyric acid (GABA) A receptor subunit, alpha 5

GABRB3

Gamma-aminobutyric acid (GABA) A receptor subunit, beta 3

GABRG3

Gamma-aminobutyric acid (GABA) A receptor, gamma 3

HMGN1

Nonhistone chromosomal protein HMG-14

MeCP2

Methyl CpG binding protein-2

RELN

Encodes Reelin, important for neuronal migration

UBE3A

Encodes ubiquitin-protein ligase E3A or E6AP ubiquitin-protein ligase (E6AP)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Bess M. Flashner
    • 1
  • Mark E. Russo
    • 1
  • Jenine E. Boileau
    • 1
  • Derek W. Leong
    • 1
  • G. Ian Gallicano
    • 1
  1. 1.Department of Biochemistry and Molecular and Cellular BiologyGeorgetown University School of MedicineWashingtonUSA

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