Why more boys than girls are autistic

[Guest guest]

Why more boys than girls are autistic

Sheryl Ubelacker The Canadian Press

Researchers are a step closer to understanding why autism spectrum disorder

affects four times as many boys as girls.

A study led by a team of Toronto scientists has discovered that males who carry

specific genetic alterations on their X-chromosome have an elevated risk for

developing autism spectrum disorder, or ASD.

“The male gender bias in autism has intrigued us for years and now we have an

indicator that starts to explain why this may be,” said co-principal

investigator Scherer, director of the Centre for Applied Genomics at

Toronto’s Hospital for Sick Children.

The researchers, whose work is published this week in the journal Science

Translational Medicine, found that about one per cent of boys with ASD had

mutations related to the PTCHD1 gene on the X-chromosome.

“Hearing that it’s in one per cent doesn’t get a lot of people excited,”

conceded Scherer. “But it gets geneticists really excited because there’s a lot

of genes involved (in ASD).”

Boys inherit one X-chromosome from their mother and one Y-chromosome from their

father, explained Scherer. “If a boy’s X-chromosome is missing the PTCHD1 gene

or other nearby DNA sequences, they will be at high risk of developing ASD or

intellectual disability.

“Girls are different in that, even if they are missing one PTCHD1 gene, by

nature they always carry a second X-chromosome, shielding them from ASD. While

these women are protected, autism could appear in future generations of boys in

their families.”

Autism spectrum disorder affects an estimated one in every 165 children. The

neurological disorder ranges in severity, but often includes problems

communicating and interacting with others, unusual patterns of behaviour and

intellectual disability.

An estimated 190,000 Canadians have ASD, which is on the rise worldwide, says

Autism Society Canada.

The isolation of genetic alterations on the X-chromosome within a percentage of

individuals with autism follows a number of recent genetic discoveries by

Scherer and others that are moving science slowly but surely towards a better

understanding of the causes of this baffling disorder.

To conduct this study, researchers analyzed the gene sequences of 2,000

individuals with ASD, along with others with an intellectual disability, and

compared the results to DNA sequencing from thousands of healthy control

subjects.

While the PTCHD1 mutation occurred in one per cent of males with ASD, it was not

present in the DNA of thousands of healthy male controls — and sisters of males

carrying the same mutation seemed unaffected by autism symptoms.

“The deletions and other mutations seem to be related only to disease in the

boys,” said co-principal researcher . “They have sisters who have

the same mutation but are healthy.”

, head of the molecular neuropsychiatry and development lab at Toronto’s

Centre for Addiction and Mental Health, isn’t surprised to find another gene on

the X-chromosome involved in autism.

“It’s another one in the list and I think it will be one of the most common

ones, so parents will be able to have their children tested,” he said.

“Particularly if they have a son affected, it will be important for them to know

if it’s caused by a mutation at or around PTCHD1.”

“And if it is, they’ll know that future (male) children would be at risk.”

“There are lots of women in the population,” added Scherer, “who are carrying

this (genetic variation) that are predisposed to having boys with autism.”

The scientists believe the PTCHD1 gene plays a role in a neurobiological pathway

that delivers information to cells during brain development, and this specific

mutation could disrupt crucial processes and contribute to the onset of autism,

said .

Having a test for the altered DNA would mean children could be diagnosed at a

younger age, allowing behavioural therapies to be started sooner, he said. “So

the earlier you can catch it, the more effective the therapies can be.”

Calling the discovery “incredibly important,” Suzanne Lanthier of Autism Speaks

said the research provides solid evidence about what’s behind ASD prevalence

rates being skewed towards males.

“This is the first time we’re seeing some hard science findings to start to

explain why boys are more affected than girls,” said Lanthier, executive

director of the research fundraising organization and mother of an 11-year-old

boy with ASD.

Asked if such genetic links to autism put an end to the contentious notion that

childhood vaccines — in particular, the measles-mumps-rubella inoculation — may

trigger autism, Lanthier responded that ASD is manifested in many ways “and it

doesn’t lay to rest potential environmental causes.”

“And what the research is pointing to more and more is that there are some

genetic underpinnings and in some cases environmental triggers that set off what

we know genetically.”

“It certainly doesn’t mean that we should stop doing research on environmental

causes. By no means.”