Gene Mutation Behind Higher Autism Rate in Boys: Study

A new study sheds light as to why boys are far more likely to be affected with autism than girls.

The new research found that males who carry specific alterations of DNA on the sole X-chromosome they carry are at high risk of developing autism spectrum disorder (ASD).

The researchers found that about one percent of boys with ASD had mutations in the patched domain containing 1 (PTCHD1) gene on the X-chromosome. Similar mutations were not found in thousands of male controls without the condition, and sisters of males carrying the same mutation are seemingly unaffected.

PTCHD1 is part of a neurobiological pathway that determines the development of human embryos. It is one of several genes recently implicated in both ASD and intellectual disabilities.

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 John Vincent, head of the Centre for Addiction and Mental Health (CAMH) Molecular Neuropsychiatry and Development Laboratory who led the study.

The researchers analyzed the gene sequences of 2,000 individuals with ASD and 246 with an intellectual disability, and compared the results with genes from more than 10,000 control individuals.

Autism is the most common condition in a group of developmental disorders known as ASDs. It is a complex neurobiological disorder that inhibits a person's ability to communicate and develop social relationships, and it is often accompanied by behavioral challenges. The Centers for Disease Control and Prevention estimates that an average of 1 in 110 children in the United States has an ASD, affecting four times as many boys as girls.

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 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 Stephen Scherer, director of The Centre for Applied Genomics at the Hospital for Sick Children.

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 said.

“While these women are protected, autism could appear in future generations of boys in their families.”

The researchers said further investigation into the PTCHD1 gene can lead to the development of novel treatments.

The research from the CAMH and the Hospital for Sick Children, both in Toronto, Canada, is published in the Sept. 15 issue of Science Translational Medicine.