New research published in The American Journal of Human Genetics has identified a previously unknown genetic link to autism spectrum disorder (ASD). The study found that variants in the DDX53 The gene contributes to ASD, providing new insights into the genetic underpinnings of the disease.
ASD, which affects more males than females, encompasses a group of neurodevelopmental conditions that result in challenges related to communication, social understanding, and behavior. While DDX53located on the X chromosome, is known to play a role in brain development and function; it was not previously definitively associated with autism.
In the study published today, researchers from the Hospital for Sick Children (SickKids) in Canada and the Istituto Giannina Gaslini in Italy clinically tested 10 people with ASD from 8 different families and found that variants in the DDX53 The gene was inherited maternally and was present in these individuals. Notably, the majority were men, highlighting the gene’s potential role in the male predominance seen in ASD.
“By pointing out DDX53 “As a key player, particularly in men, we can better understand the biological mechanisms at play and improve diagnostic accuracy for individuals and their families,” says lead author Dr. Stephen Scherer, Senior Scientist of Genetics and Genome Biology. and Head of Research at SickKids. and Director of the McLaughlin Center at the University of Toronto.
“The identification of this new gene as a confirmed contributor to ASD underscores the complexity of autism and the need for comprehensive genetic analysis.”
At the same location on the X chromosome, the researchers found evidence that another gene, PTCHD1-AScould be involved in autism. The study highlights a case in which a child and his mother, both with autism and low support needs, had a specific genetic deletion that led to the DDX53 gene and parts of PTCHD1-AS.
The study cohort was assembled through an international collaborative effort, involving several renowned clinical and research institutions in Canada, Italy, and the US. Further analysis of large autism research databases, including Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, identified 26 additional people with ASD. that had similar rare DDX53 variants to the study participants.
“This gene has eluded us for a long time and has not previously been linked to any neuropsychiatric conditions. Our findings support a direct link between DDX53 and autism, which is not only crucial for future clinical genetic testing, but its discovery suggests that the pathway it affects is related to the behavioral traits of autism, opening up a whole new area of exploration,” says the lead author, Dr. Marcello Scala, researcher in Medical Genetics at the Istituto Giannina Gaslini, affiliated to the University of Genoa (Department of Neuroscience).
In another paper published today in the same journal, Scherer and lead author Dr. Marla Mendes, a SickKids researcher, identified 59 genetic variants on the X chromosome significantly associated with ASD. The variants were found in genes linked to autism, including PTCHD1-AS (nearly DDX53), DMD, HDAC8, PCDH11X, and PCDH19 along with new candidates linked to TEA ASB11 and ASB9. Furthermore, the FGF13 The gene was highlighted as being linked to ASD, with sex-specific differences, adding further evidence for the role of sex chromosomes in the condition.
“These findings provide new insights into the biology of the X chromosome in ASD, providing additional evidence for the involvement of certain genes such as DDX53 and FGF13and we suggest that they be investigated further,” says Scherer.
The team points out that the absence of a gene similar to DDX53 in commonly used mouse models may require future researchers to reconsider how they study ASD. Since it lacks a functional equivalent in these models, the findings in DDX53 It cannot be easily replicated.
“Insights from this study could significantly influence the design and interpretation of autism research, particularly the development of new models. Identifying these variants is an important step toward developing more accurate diagnoses and therapies for patients and families.” with ASD,” says Scherer.
Scherer also added that “both studies provide even more evidence that complex neurobehavioral conditions like autism can sometimes have simple biological (genetic) underpinnings.”
The study was funded by the McLaughlin Center at the University of Toronto, Autism Speaks, Autism Speaks Canada, Ontario Brain Institute, the Italian Ministry of Education, University and Research and the SickKids Foundation. Additional funding was provided by the National Institutes of Health and the UCLA California Center for Rare Diseases.