The Burrill Report


Researchers at the Centre for Addiction and Mental Health and The Hospital for Sick Children, both in Toronto, have discovered that males who carry specific mutations of DNA on the sole X-chromosome they carry are at high risk of developing Autism Spectrum Disorder or ASD, a condition that affects four times more males than females.

ASD is a neurological disorder that affects brain functioning, resulting in challenges with communication and social interaction, unusual patterns of behavior, and often, intellectual deficits. ASD affects one in every 120 children and one in 70 boys. Though all of the causes of ASD are not yet known, research has increasingly pointed towards genetic factors and several genes involved in the disorder have already been identified.

In the current research, scientists analyzed the gene sequences of 2,000 individuals with ASD, along with others with an intellectual disability, and compared the results to thousands of population controls. The study, published in Science Translational Medicine, found that about 1 percent of boys with ASD had mutations in the PTCHD1 gene on their X-chromosome. Similar mutations were not found in thousands of male controls. Also, sisters carrying the same mutation appear unaffected.

“We believe that the PTCHD1 gene has a role in a neurobiological pathway that delivers information to cells during brain development–this specific mutation may disrupt crucial developmental processes, contributing to the onset of autism,” says John Vincent, lead researcher and head of the Centre for Addiction and Mental Health’s Molecular Neuropsychiatry and Development Laboratory. “Our discovery will facilitate early detection, which will, in turn, increase the likelihood of successful interventions.”

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, says research team member Stephen Scherer, director of The Centre for Applied Genomics at SickKids, and director of the McLaughlin Centre at the University of Toronto.

Boys inherit one X-chromosome from their mother and one Y-chromosome from their father. 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 an intellectual disability, says Scherer. For girls, even if they are missing one PTCHD1 gene, they always carry a second X-chromosome, which shields them from ASD. While these women are protected, autism could appear in future generations of boys in their families, notes Scherer.

Researchers hope further investigation into the PTCHD1 gene will also indicate potential avenues for new therapy.




September 22, 2010
http://www.burrillreport.com/article-missing_dna_in_boys_linked_to_autism.html