Genetics and Mitochondrial Abnormalities in Autism Spectrum Disorders:A Review

Sukhbir      Dhillon; Jessica      A. Hellings; Merlin      G. Butler

Abstract

We review the current status of the role and function of the mitochondrial DNA (mtDNA) in the etiology of autism spectrum disorders (ASD) and the interaction of nuclear and mitochondrial genes. High lactate levels reported in about one in five children with ASD may indicate involvement of the mitochondria in energy metabolism and brain development. Mitochondrial disturbances include depletion, decreased quantity or mutations of mtDNA producing defects in biochemical reactions within the mitochondria. A subset of individuals with ASD manifests copy number variation or small DNA deletions/duplications, but fewer than 20 percent are diagnosed with a single gene condition such as fragile X syndrome. The remaining individuals with ASD have chromosomal abnormalities (e.g., 15q11-q13 duplications), other genetic or multigenic causes or epigenetic defects. Next generation DNA sequencing techniques will enable better characterization of genetic and molecular anomalies in ASD, including defects in the mitochondrial genome particularly in younger children.

Keywords: Autism spectrum disorders (ASD), mitochondrial DNA (mtDNA) mutations and depletion, oxidative stress, nuclear genes, lactate/pyruvate ratios, genetic causation, copy number variation, Heteroplasmy, nucleotide polymorphisms, fragile X syndromes