New studies have uncovered previously unrecognized genetic factors associated with autism spectrum disorder (ASD), offering fresh perspectives on the genetic basis of this condition.
Recent research featured in The American Journal of Human Genetics has discovered a novel genetic connection to autism spectrum disorder (ASD). The investigation revealed that variations in the DDX53 gene play a role in ASD, shedding light on the genetic foundations of the disorder.
ASD, which occurs more frequently in males than females, includes a variety of neurodevelopmental disorders that present difficulties in communication, social skills, and behavior. The DDX53 gene, located on the X chromosome, is already known to be involved in brain development and function, but was not previously clearly linked to autism.
In this newly published study, researchers from The Hospital for Sick Children (SickKids) in Canada and Istituto Giannina Gaslini in Italy conducted clinical assessments on 10 individuals with ASD from 8 distinct families. They discovered that mutations in the DDX53 gene were inherited from their mothers and were present in these individuals. Interestingly, the majority of the cases were male, indicating a potential relationship between this gene and the male predominance seen in ASD.
“By identifying DDX53 as a significant factor, especially in males, we can enhance our understanding of the biological mechanisms involved and improve diagnostic precision for those affected and their families,” stated Dr. Stephen Scherer, senior author of the study, who is a Senior Scientist at SickKids and the Director of the McLaughlin Centre at the University of Toronto.
“This discovery of a new gene as a confirmed factor in ASD highlights the complexity of the disorder and the importance of thorough genetic analysis.”
The researchers also found indications that another gene, PTCHD1-AS, at the same location on the X chromosome, may be associated with autism. They noted a case of a boy and his mother, both diagnosed with autism and requiring minimal support, who exhibited a specific deletion of genes that included DDX53 and parts of PTCHD1-AS.
The study participants were gathered through an international collaborative effort among several prestigious clinical and research institutions from Canada, Italy, and the U.S. Additional examination of extensive autism research databases such as Autism Speaks MSSNG and Simons Foundation Autism Research Initiative revealed 26 more individuals with ASD exhibiting similar rare variants of the DDX53 gene as those studied.
“This gene has been elusive and not linked to any neuropsychiatric condition up until now. Our results indicate a direct association between DDX53 and autism, which is not just vital for future clinical genetic assessments but also suggests that the biological pathways it influences relate to autistic behaviors, opening new avenues for research,” explained Dr. Marcello Scala, lead author and researcher in Medical Genetics at Istituto Giannina Gaslini, which is affiliated with the University of Genoa (Department of Neuroscience).
In another article released today in the same journal, Scherer and lead author Dr. Marla Mendes, a research fellow at SickKids, reported on 59 genetic variants located on the X chromosome that showed a significant correlation with ASD. These variants were linked to genes associated with autism, such as PTCHD1-AS (near DDX53), DMD, HDAC8, PCDH11X, and PCDH19, in addition to new ASD-associated candidates like ASB11 and ASB9. Furthermore, the study highlighted the FGF13 gene as related to ASD, with gender-specific differences, providing further evidence regarding the influence of sex chromosomes in the disorder.
“These findings offer fresh insights into the biology of the X chromosome concerning ASD, reinforcing the potential involvement of specific genes such as DDX53 and FGF13, suggesting they merit further investigation,” remarked Scherer.
The research team pointed out that the absence of a gene similar to DDX53 in widely used mouse models may necessitate a reevaluation of how ASD is studied in the future. Since these models lack a functional equivalent to DDX53, findings regarding this gene cannot be easily replicated.
“The insights gained from this study could greatly impact the design and interpretation of autism research, especially in the creation of new models. Identifying such variants is a crucial step toward developing more accurate diagnostics and treatments for families dealing with ASD,” Scherer noted.
Scherer also mentioned, “Both studies present even greater evidence that complex neurobehavioral conditions like autism can sometimes stem from straightforward biological (genetic) causes.”
The study received funding from the University of Toronto McLaughlin Centre, Autism Speaks, Autism Speaks Canada, Ontario Brain Institute, the Italian Ministry for Education, University and Research, and SickKids Foundation. Additional financial support was provided by the National Institutes of Health and the California Center for Rare Diseases at UCLA.
