Aspies For Freedom

GENETIC RESEARCH

Study reveals DNA clue to cause of condition
Jan 18, 2008 04:30 AM
Megan Ogilvie
Health Reporter

In many ways, that Tuesday evening phone call did not change much for the Bond family.

Stewart Bond still goes to work at IBM every day and walks their dog, Misty, around their Stouffville neighbourhood at night. His wife, Lisa, still runs errands, cooks dinner and plans fun outings with their daughter, Rebecca. And their son, Joshua, still has autism.

But now, because of that phone call from researchers at The Hospital for Sick Children, the Bonds know why Joshua, an often-giggling, book-loving, Transformers-obsessed 11-year-old, has the disorder. And that, they say, has changed their life.

"Because there is very little known about the causes of autism, you get that diagnosis, and you ask yourself if it was because of something that you did," says Stewart. "And now we understand that it's not. ... there's no thinking about that at all."

The Bonds are one of only four families in Canada who know their child's autism is due to a genetic error on his 16th chromosome. Joshua, who was diagnosed with autism at 6, is missing a short string of DNA on a specific region of this chromosome, and it's this teeny nick that makes it hard for him to pronounce certain words, to get accustomed to new foods and sometimes to interact with strangers.

The family is one of the first to get this definitive diagnosis because they, along with about 400 other families, have been involved in a long-term study at Sick Kids that is searching for the genetic roots of autism, one of the most common and debilitating developmental disorders in children.

The results of that study, published yesterday in the American Journal of Human Genetics, revealed that genetic mistakes along a segment of chromosome 16 appear to increase a child's risk of developing autism by as much as a hundred-fold.

These errors – deleted or duplicated pieces of DNA, called copy number variation – are relatively rare, accounting for only 1 per cent of autism cases, says Stephen Scherer, lead author of the paper and senior scientist at Sick Kids.

This genetic hot spot was also identified by two other research groups, including the Boston-based Autism Consortium that published results last week.

The errors on chromosome 16 are usually spontaneous genetic mutations not passed down from parents to children. Of the four people in the study with the mutation, only one inherited it from a parent.

The next step, already underway at Sick Kids, is to develop a simple and inexpensive DNA test that can pinpoint duplications or deletions on chromosome 16. Right now, autism is diagnosed by assessing a child's behaviour and social communication skills, an often difficult and labour-intensive process, says Rosanna Weksberg, a clinical geneticist and head of clinical and metabolic genetics at Sick Kids.

A DNA test performed as soon as a child exhibits some symptoms could catch autism quickly and early, she says. Studies have shown early intervention, especially when an infant's brain is still developing, can diminish some symptoms.

The promise of genetic tests also raises ethical considerations that researchers are just starting to sort out. For example, how would a potential prenatal DNA test for chromosome 16 mutations be used in family planning?

Wendy Roberts, a developmental pediatrician and co-director of the Autism Research Unit at Sick Kids, says even a DNA test of parents would be valuable for predicting the chances of their next child having autism. If the parents do not test positive for the mutation, the likelihood of a second child testing positive is no higher than in the general population, she says. And she knows there is demand for it; the hospital is already fielding calls from parents who have heard about the mutation and want the test.

"If they thought there would be a test available within a year, most (parents wanting another child) would wait that long," she says.

For other families, just knowing a small DNA blip caused their child's autism will be enough. Though the diagnosis doesn't change, the way they understand it will. "It has a very positive effect on the whole family dynamic," says Weksberg.

The Sick Kids team hopes that as researchers continue to plumb the genome, further markers of autism will appear. They've known for a long time that it's a complex disorder and this is just the first fruit of a long struggle to untangle it.

Last year, Scherer co-authored a study that showed as many as 100 genes could be involved or work in combination to cause autism. Previously, scientists believed only 20 genes caused the disorder.

Lisa Bond knows in the big picture the chromosome 16 mutation is one small piece of a larger mystery. But for her family, she says, it's a big, big piece of the puzzle.

In the week after receiving the news about Joshua, the Bonds have tried to make sense of their new peace – and find the best way to tell Joshua himself.

"We don't want him to think that something was missing, that he has a piece missing," says Lisa. "So we explain things to him in another way."

They have told him that he is extra-special, that he is a hero for helping other kids know why they have autism. "I think he thinks that's pretty cool," she laughs. "And in our eyes, he is extra-special."