Additional insight into why autism spectrum disorder (ASD) affects males four times more often than females was gained through the results of a new study for the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids), Toronto, Canada, which were published last week in Science Translational Medicine.

Led by Dr. John B. Vincent, Senior Scientist and head, Molecular Neuropsychiatry and Development Laboratory, CAMH, and Dr. Stephen Scherer, Senior Scientist and Director, The Centre for Applied Genomics, SickKids, and Director, McLaughlin Centre, University of Toronto, the researchers found that males who carry specific DNA alterations on their single X-chromosome are at high risk for developing ASD,

After analyzing the gene sequences of 2,000 participants with ASD, other participants with an intellectual disability, and thousands of population controls, the team found that roughly 1% of boys with ASD “had mutations in the PTCHD1 gene on the X-chromosome,” whereas sisters of theirs with the same mutation remained seemingly 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.” said Dr. Vincent. “Our discovery will facilitate early detection, which will, in turn, increase the likelihood of successful interventions."

Adding to Vincent’s sentiments, Scherer said “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. Boys are boys because they 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 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."