TORONTO - Canadian-led research has discovered numerous DNA regions containing gene abnormalities that appear to make children susceptible to autism spectrum disorder, a finding that could help parents get an earlier diagnosis for some kids with the disorder.
Senior investigator Stephen Scherer said these genetic anomalies were found in seven per cent of 427 unrelated children with autism spectrum disorder (ASD), representing 13 different regions of the genome.
Similar deletions and duplications of genes were not detected in parents of the children, meaning they were not inherited, said Scherer, director of the Centre for Applied Genomics at Toronto's Hospital for Sick Children. The missing or extra genes would have arisen spontaneously in the children, likely at conception or in early fetal growth.
"So one of the messages is there's probably a lot of genes involved in autism and in seven per cent of the cases we'll be able to capture some information that will be clinically relevant for the families to know," he said.
The research was published online Thursday by the American Journal of Human Genetics.
Scherer said hospital autism clinics should begin testing children with a suspected case of the disorder for any of these genetic aberrations as early in childhood as possible. Sick Kids is in the process of developing such a test program in its autism clinic.
A prenatal test could also be developed to look for these genetic changes, he said.
Autism is a complex and baffling developmental disorder that occurs in about one in every 165 children. Depending on its severity, kids with ASD may have difficulty with social interaction, have language and learning disabilities, and engage in repetitive behaviours.
Finding out as early as possible whether a child has an autism spectrum disorder would not only give an answer sooner to worried patients, but would also mean getting their youngster started sooner in programs to help mitigate behavioural and learning problems associated with ASD.
Early intervention has been shown to dramatically improve an autistic child's ability to deal with the effects of the disorder.
Lisa Bond said she and her husband started realizing something was not quite right with their son Joshua when he just over a year old. But it took another five years or so for him to be definitively diagnosed with autism.
"When he was very small he wouldn't make eye contact, he couldn't communicate, he'd get upset at the least little thing, like change the colour of his socks and this kid could scream for hours," recalled Bond of Stouffville, Ont., northeast of Toronto.
What was also frustrating is that while he had some behaviours typical of ASD, others were not - and no one could explain why or what that meant, said Bond, who also has a 14-year-old daughter.
"He has speech and motor issues and everything else, which is common for kids with autism, but a lot of them tend to either catch up or whatnot. We started noticing things that really concerned us and there were a few things that didn't seem typical with him."
It turns out that Joshua, who turns 12 next week, is among one per cent of autistic kids with a gene deletion on chromosome 16, one of the anomalies recently found by Scherer's group and other labs.
International research is now focusing on how such a change might correspond with specific neurological symptoms common to all kids carrying that genetic deletion or addition.
Missing genes in chromosome 16 appears to cause the more severe speech difficulties that have afflicted her son, Bond said, adding that Joshua's autism specialist told her: "Now you know that some of the difficulties he has been having are related to this deletion. Now you know and you can go on to help him."
While that doesn't mean the problems can be "fixed," Bond said understanding what underlies them can help the family improve Joshua's quality of life.
"It's a real gift. It might be a small piece in the research, but it's huge for us. It's life-changing for us and our son."
Mark Daly, an assistant professor at the Harvard School of Medicine, said Scherer and his team have been leaders in analyzing and cataloguing genetic mutations known as "copy number variations" - and pinpointing more regions where these occur in autism cases advances scientists' knowledge about the what may cause the disorder.
"So I think this certainly suggests that there's more to be found and more to be learned through this line of inquiry," said Daly, whose lab also is researching the genetics behind autism.
Larger databases of DNA from families with autism need to be analyzed to see how often mutations occur in these 13 regions of the genome, he said Thursday from Boston.
"Even if we can just confirm in a small number of families some of these specific events that this study has identified, they may provide us more of the biological clues to autism."
In some of the Canadian autism cases studied, Scherer and his team found malformations in genes already known to be involved in neurological function, and they identified at least two sites in the DNA previously linked to mental retardation.
Knowing whether a non-inherited chromosomal alteration has occurred in a child with autism helps alleviate parents' fear of having another child - one more reason for making genetic testing available through autism clinics, he said.
"The most important thing is it tells the family that this is the likely contributing factor, so it takes away any blame there might be that: 'I did something wrong in my pregnancy,"' said Scherer. "There's a random chance in all of our DNA, mine and yours and everybody else's. In this case, it just happened to hit genes that are involved in probably neurological development."
"It's a different way of looking under the hood, and if it adds more information it should be available to the families."
Bond said having such a test would be a huge boon for at least some parents waiting anxiously for a definitive diagnosis for their child.
"Maybe someday parents won't have to hear, 'We don't know.' Now a select group of them will be able to hear, 'You know what, we do know."'
