New Research Links Gene Mutations To Autism

Researchers reported in the journal Nature on Wednesday that about 15 percent of autism cases in families with a single autistic child are associated with spontaneous mutations that occur in six cells.

Several papers published in the April 4 issue of the journal show how gene mutations may contribute to the development of autism.

For the studies, the researchers sequenced the DNA of about 1,000 families, each of which had an autistic child.

The gene mutations identified in the study were discovered with a new genomics technology known as exome sequencing.

One group of researchers from Yale University said that with further characterization of the genes and sequencing of genes in thousands of families, they will be able to develop novel therapeutics and preventive strategies for autism.

“We now have a good sense of the large number of genes involved in autism and have discovered about 10 percent of them,” Joseph Buxbaum, PhD, Director of the Seaver Autism Center, said in a statement. “We need to study many more parents and their affected children if we are to uncover the genes important in ASD. As these genes are further characterized, this will lead to earlier diagnosis and novel drug development.”

The studies all found that de novo mutations account for a substantial fraction of the risk for autism.  These types of mutations show up in affected children for the first time and result from mutations in the production of sperm or egg.

“When the same mutations are found in multiple affected children and none are found in children without autism, we believe that we have identified mutations that collectively affect a higher proportion of individuals with autism,” Buxbaum said in a press release.

Researchers found that less than half of the autism cases studied carried a potentially protein-altering de novo point mutation.

“These data suggest that there is a role for de novo point mutations in the coding region of the genome for autism, but they do not constitute a sufficient cause,” Benjamin Neale, a research affiliate at the Broad Institute and an assistant in genetics at MGH, said in a press release. “That is to say, most de novo variants do not fully explain the disorder in an individual.”

The researchers were also able to link variations in three specific genes to a markedly increased risk for autism.

“Prior to the advent of new DNA sequencing technology, we were largely wandering in the dark searching for autism genes,” Matthew State, senior author of one of the papers, said in a press release. “Now we are getting a clear view of the genetic landscape and finally have the tools in hand to find a large proportion of the many genes contributing to autism.”

Studies involving twins also helps reveal a strong genetic component to autism, but a large number of cases occur in families that have not had a history with the condition.

The Yale study found that de novo mutations were more frequently in children born to older fathers, offering a partial explanation for the increased risk for autism in children of older parents.

The team believes that the percentage of autism cases linked to these de novo mutations will increase.

“With every new gene we discover, we learn more about potential treatments for patients with autism,” Stephan Sanders, lead author of one of the papers in Nature, said in a press release.