Link to autism in boys found in missing DNA

New research from the Centre for Addiction and Mental Health (CAMH) and The Hospital for Sick Children (SickKids), both in Toronto, Canada provides further clues as to why Autism Spectrum Disorder (ASD) affects four times more males than females. The scientists discovered that males who carry specific alterations of DNA on the sole X-chromosome they carry are at high risk of developing ASD. The research is published in the September 15 issue of Science Translational Medicine.

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

The research team was led by Dr. John B. Vincent, Senior Scientist and head of CAMH's Molecular Neuropsychiatry and Development Laboratory and Dr. Stephen Scherer, Senior Scientist and Director of The Centre for Applied Genomics at SickKids, and Director of the McLaughlin Centre at the University of Toronto. The 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. They found that about one per cent of boys with ASD had mutations in the PTCHD1 gene on the X-chromosome. Similar mutations were not found in thousands of male controls. Also, sisters carrying the same mutation are 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."

"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 Dr. Scherer. "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." Scherer adds, "While these women are protected, autism could appear in future generations of boys in their families."

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

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The funding to the Canadian team came from public and private partners including major awards and support from Autism Speaks, Genome Canada through the Ontario Genomics Institute, the McLaughlin Centre, the Canadian Institutes of Health Research (CIHR), the Canadian Institute for Advanced Research, the Canada Foundation for Innovation, Ontario's Ministry of Research and Innovation, the Ontario Innovation Trust, the Catherine and Maxwell Meighen Foundation, the National Alliance for Research on Schizophrenia and Depression, the Ontario's Premier's Summit Award in Medical Research, The Centre for Applied Genomics, the Chedoke Health Corporation, the Mayberry Family Fund, the Hamilton Health Sciences Foundation and the SickKids Foundation.