Medical News Observer

Cornell University researchers have confirmed a genetic link between mitochondrial DNA (mtDNA), which is passed on from the mother, and some forms of autism spectrum disorder (ASD). Previous research suggested a link between mitochondrial functional defects and autism spectrum disorder, but those studies included small sample sizes and could not verify whether the cause was genetic or environmental.

The current study, published Oct. 28 in the journal PLOS Genetics, analyzed mitochondrial DNA in 903 families, where the researchers compared the mitochondrial DNA of an affected child and an unaffected sibling and their mother. They found that in instances when the children had both mutant and normal mitochondrial DNA in a single cell, called heteroplasmy, all the children showed similar numbers of mutant mitochondrial DNA, but the autistic children had more than twice as many harmful mitochondrial DNA (mtDNA) mutations compared to their non-autistic siblings.

“We show not only that mitochondrial DNA heteroplasmy is associated with autism, but also, among autistic kids, these pathogenic mitochondrial DNA mutations are significantly associated with intellectual disability, and other neurological and developmental defects,” said Yiqin Wang, a graduate student in Gu’s lab and the paper’s first author.

The current findings may lead to better diagnosis and treatment of children with a sub-type of autism caused by pathogenic mitochondrial DNA (mtDNA) mutations. Analyzing mitochondrial DNA could help diagnose some forms of autism in the future. Interventions restoring mitochondrial function might also be useful for treatment, Gu said. These findings also have relevance for other childhood neurodevelopmental disorders, which may be caused by disease-causing mitochondrial DNA mutations and is a subject for future work, he said.

During egg production, there is a dramatic reduction in the numbers of copies of mitochondrial DNA (mtDNA), as a way of eliminating bad mutations passed from mother to child. But some bad mutations still pass to the next generation, and the number of pathogenic mitochondrial DNA in children may be affected by the mother’s environment or physiology, Gu said.

“Does the mother have inflammation or diabetes, or is she obese?” Gu said. “These things could make the process of cleaning up mutations less efficient. This could give us some insight into why autism is rising,” and will be a subject for future studies, Gu said.

Future work will also include looking into the effects of environment, diet and the mother’s health on mitochondrial DNA in children, Gu said. The group is also developing better tools for efficient and cost-effective mitochondrial DNA sequencing, he said.

Citation: Wang, Yiqin, Martin Picard, and Zhenglong Gu. “Genetic Evidence for Elevated Pathogenicity of Mitochondrial DNA Heteroplasmy in Autism Spectrum Disorder.” PLOS Genetics 12, no. 10 (2016): e1006391.
DOI: http://dx.doi.org/10.1371/journal.pgen.1006391
Research funding: Cornell University, National Science Foundation, National Institutes of Health, ENN Science and Technology Development Company.
Adapted from press release by Cornell University