Beyond Genes: Germline Disruption in the Etiology of Autism Spectrum Disorders

Document Type

Article

Publication Date

10-2022

Journal Title

Journal of autism and developmental disorders

MeSH Headings

Anesthetics, Inhalation; Autism Spectrum Disorder (genetics); Autistic Disorder (genetics); Germ Cells; Humans; Valproic Acid

Abstract

Investigations into the etiology of autism spectrum disorders have been largely confined to two realms: variations in DNA sequence and somatic developmental exposures. Here we suggest a third route-disruption of the germline epigenome induced by exogenous toxicants during a parent's gamete development. Similar to cases of germline mutation, these molecular perturbations may produce dysregulated transcription of brain-related genes during fetal and early development, resulting in abnormal neurobehavioral phenotypes in offspring. Many types of exposures may have these impacts, and here we discuss examples of anesthetic gases, tobacco components, synthetic steroids, and valproic acid. Alterations in parental germline could help explain some unsolved phenomena of autism, including increased prevalence, missing heritability, skewed sex ratio, and heterogeneity of neurobiology and behavior.

First Page

4608

Last Page

4624

Link to Full Text

Share

COinS