A small number of autism cases are linked to a gene found on the X chromosome, a discovery that may help explain why boys are four times more likely than girls to develop the disorder.
There is no one gene responsible for autism spectrum disorder, or ASD.
People with the disorder may have mild to severe symptoms that inhibit a person's ability to communicate and develop social relationships, which is often accompanied by behavioural challenges. In some people the disorder has a strong inherited component.
Now, in Wednesday's online issue of the journal Science Translational Medicine, researchers at Toronto's Hospital for Sick Children, the Centre for Addiction and Mental Health and others report specific genetic alterations on the X chromosome that increase the risk of developing autism.
Females carry two copies of the X chromosome, so they have a backup. Males, however, have only one X from their mothers and one Y from their fathers.
So males who would inherit the genetic change from their mother are not protected, said the study's co-senior author, Prof. Stephen Scherer, senior scientist and director of the Centre for Applied Genomics at SickKids.
About one in 70 baby boys will develop ASD, Scherer said in an interview.
"So we've now identified the genetic cause in one per cent of those individuals, so in fact it's actually a large proportion of the population," Scherer said, meaning this newly identified mutation likely accounts for the biggest proportion of genes associated with autism.
The newly identified change is found on a gene called Patched 1 or PTCHD1.
Test in works
To find it, researchers analyzed the genomes of almost 2,250 individuals, including almost 2,000 with ASD and 246 with intellectual disabilities, as well as more than 10,000 controls.
The gene is thought to play a role in neurobiological pathways that deliver information to cells during brain development, the researchers said.
If the change is identified on the X chromosome and it is passed on to a boy, which would occur in about half of cases, the likelihood that he will be autistic is very high, said Scherer.
With the latest discovery, a genetic alteration that leads to autism could be identified in about 15 per cent of families with autism, Scherer noted.
Blood or saliva tests based on the discovery will probably roll out in the next year in most places, he predicted.
Its important to communicate the information to families, because they often ask what is the cause of autism in their family, or they want to know the risk of it occurring in another child or relative, Scherer said.
Raises 'heartbreaking' idea
Katrina and Scott Carefoot of Oakville, Ont., say if a test had been available sooner, their four-year-old autistic son Max would have been diagnosed and treated earlier. He was diagnosed 18 months ago.
The couple also sees the potential downside: if there'd been a prenatal test, they'd likely have ended the pregnancy.
"The idea of not having him is heartbreaking," his mother said. "Sometimes I think maybe it's better not to know in advance if it means that you wouldn't proceed, because the idea of not having him crushes me."
The weakness of a "yes or no" diagnostic test is that it can't show the degree of disability for a disorder that ranges from barely discernible to completely debilitating, said Andrew Fenton of the bioethics department at Dalhousie University in Halifax.
"There's lots of confusion there about the quality of life for someone on the spectrum that won't be answered by genetic tests," Fenton said. "My primary worry would be that parents would be making this decision based on those misunderstandings."
Unravelling the genetic and biological basis for autism is important, even though these findings explain only a small proportion of ASD patients, said Dr. Michael Hayden, Killam professor of medical genetics at the University of British Columbia.
At this point, the findings offer diagnostic but not therapeutic hope, Hayden said Wednesday.
"Its an important step, but it's just the first step in trying to elucidate the pathways involved," Hayden said from Toronto.
The next step for researchers will be to try to understand how the genetic information fits in the symptoms they see in patients, added Hayden, who is also the director of the Centre for Molecular Medicine and Therapeutics in Vancouver.
The study was also funded by Genome Canada through the Ontario Genomics Institute, the McLaughlin Centre, the Canadian Institutes of Health Research, the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, Ontario's Ministry of Research and Innovation, the Ontario Innovation Trust, the Catherine and Maxwell Meighen Foundation, the National Alliance for Research on Schizophrenia and Depression, the Ontario's Premier's Summit Award in Medical Research, the Centre for Applied Genomics, the Chedoke Health Corporation, the Mayberry Family Fund, the Hamilton Health Sciences Foundation and the SickKids Foundation.