A comparative genomic hybridization (CGH) analysis of the DNA from an autism spectrum disorder (ASD) lymphoblastoid cell line has revealed multiple copy number variants (CNVs) that impact nuclear DNA (nDNA) mitochondrial genes, with many of the CNVs found within the mitochondrial genes. Alterations in the mitochondrial DNA (mtDNA) were also found. To determine if a subset of ASD is caused by mitochondrial dysfunction, this research will survey patient lymphoblastoid cell lines for those harboring nDNA CNVs or mtDNA mutations that alter mitochondrial genes. Cell lines from patients with the mutations will be tested for the expected mitochondrial function. If mitochondrial defects are found, selected patients will be tested using non-invasive biophysical and biochemical tools to determine if they manifest a functional mitochondrial defect. Demonstration that a subset of ASD patients harbor mitochondrial defects would suggest new approaches for the treatment of this class of ASDs.