Autism link to mutations in mitochondria

Children with autism spectrum disorder (ASD) have twice as many harmful mutations in their mitochondrial DNA (mtDNA) as their siblings, a study has found.

The link was strongest in those children who had the most pronounced intellectual and social deficits.

'When we compared the inheritance between the mother and the children, we confirmed this particular pattern, which is the child with autism inherited more bad mutations than their siblings during the process of passing mitochondrial DNA from mother to children,' said senior author Dr Zhenglong Gu of Cornell University, who led the research, published in PLOS Genetics.

Previous studies had suggested a link between mutated mtDNA and the risk of developing ASD, so the researchers sequenced mtDNA from 903 families with one ASD-affected child. They compared the mtDNA of children affected by ASD with their unaffected siblings and with their mothers (mitochondrial DNA is only inherited from the mother).

In cells which had both mutant and normal copies of mtDNA, there were similar amounts of mutant mtDNA in the children with ASD and their siblings. But the children with ASD had more than twice the number of harmful mutations compared with their unaffected siblings or their mother.

Mitochondria provide energy for the cell, and each cell carries hundreds of copies of their own mtDNA. Unlike nuclear DNA, mtDNA mutates very rapidly – mutations are passed on from mother to the child, but can also occur spontaneously. There are differences between siblings in how much mutated mtDNA they inherit from their mother, as more can end up in one egg cell than another during meiosis.

When they included information about the child's IQ, social responsiveness and other clinical features, they found more cells containing mutant mtDNA and higher levels of harmful mutations in the children with the most pronounced ASD symptoms.

The researchers hope that further research into the mechanism of mitochondrial mutations may help improve diagnosis and treatment in a subset of ASD cases.

'Ultimately, understanding the energetic aspects of neurodevelopmental disorders may lead to entirely new kinds of treatments, and preventative strategies that would target mitochondria,' said Dr Gu.