SickKids study identifies genetic pathway tied to autism behaviours

Chief of Research at SickKids Steve Scherer says the findings of a new study could potentially lead to precision therapeutics for all autism diagnoses.

A newly identified genetic pathway linked to autism spectrum disorder could help scientists better understand the condition’s core social and behavioural traits, according to a major Canadian-led study published Wednesday in the journal Nature.

Researchers at Toronto’s Hospital for Sick Children found that a non-coding gene, known as PTCHD1-AS, on the X chromosome was associated with autism in males who carried small deletions in the gene.

“We’ve known for many years now that genetics plays a key role in the development of autism spectrum disorder or autism,” Stephen Scherer, chief of research at SickKids, said in an interview with CTVNews.ca, adding that the study followed more than 10,000 families over 15 years.

Scientists have already identified around 100 genes linked to autism, but most of them are protein-coding genes, meaning they provide instructions for making proteins in the body and brain.

They are also associated with a broad range of developmental and medical conditions, including intellectual disability, epilepsy and ADHD.

“They account for roughly 20 per cent of those people that have a diagnosis of autism, and those individuals tend to be profoundly affected, so they have additional medical complications in addition to the core features that we see in all autism diagnoses,” Scherer said.

But he said this study focused on a different, less understood type of gene known as a non-coding RNA gene.

Unlike many previously identified autism-linked genes, the researchers say this one appears specifically tied to the condition’s hallmark traits, including social communication differences and repetitive behaviours, without affecting learning, memory or attention.

“There are individuals, in particular males, that have deletions of a small segment of DNA in this RNA encoding gene,” Scherer explained. “In every case, when we find those deletions, they have a form of autism and it’s typically the non-syndromic form. Those individuals only have their social behavioural and their communication and their stereotypic behaviours impacted.”

‘A biological trait’

Autism spectrum disorder, or ASD, affects roughly one in 50 children and youth in Canada.

In the new study, researchers analyzed whole-genome sequencing data from more than 9,300 people with autism and more than 8,300 people without the condition.

They identified 27 males with autism who had tiny missing pieces of DNA, known as microdeletions, in the PTCHD1-AS gene.

The gene is located on the X chromosome, which researchers say may help explain why the findings were seen almost entirely in males.

“Females have a backup X chromosome, so they’re protected in a way, and often we actually see that moms are passing a deletion of this to a boy , and if that’s the case, then they have an autism diagnosis,” Scherer said, adding that identifying a specific biological pathway could eventually help researchers develop more targeted therapies.

“The simplest is to take a pill, so a medication that’s designed to modulate a genetic pathway,” he said. But he stressed the research is not about “curing” autism.

“Autism is a biological trait,” Scherer said. “We’re trying to provide more options for decisions for the family to make.”

He said the findings could also improve early identification through genetic testing and help families better understand why autism occurs.

“The No. 1 question that we’re asked by families that have a family member with autism is: ‘What is the reason autism came about in my son or my sister or my brother?” Scherer said.

“With these new genetic studies we’ve been performing now for several decades, we can actually give an answer to about 20 per cent of those families,” he added. “When we started this, it was zero per cent.”

Scherer said the findings may also deepen scientific understanding of how small genetic changes can shape human behaviour.

“It’s really amazing to me as a scientist to think about how hard-wired we are as a species.”