Autism Genome Project issues new guide urging CNV-based genetic testing

April 24, 2014

Researchers with the Autism Genome Project are calling for widespread adoption of genetic testing based on copy number variantions (CNVs) – to advance toward individualized diagnosis and treatment of autism.

US-based Autism Speaks described the recommendation as being part of the AGP’s largest-ever study, published today in the American Journal of Human Genetics. "The report delivers on the 10-year-old project’s goal of providing practical methods for earlier diagnosis and personalized treatment of autism," reports a story on Autism Speaks' website.The organization is a primary funder of the Autism Genome Project, which involves more than 50 research centers in 11 countries, including the work of NeuroDevNet ASD research group co-lead, Dr. Stephen Scherer at the University of Toronto.

“This report and its extensive supplements should become a new guidebook for medical geneticists working with families affected by autism,” said Dr. Scherer, co-discoverer of CNVs, genetic changes involving duplication or deletion of segments of DNA that a growing number of studies are linking with ASD.

Why is CNV-based testing important?
Standard genetic tests used to help diagnose autism don't pick up CNVs. Instead, most medical genetic testing looks for “spelling mistakes” in the DNA letters that compose a specific gene. Such standard testing identifies a clear genetic cause for autism only 15 to 20 percent of the time.

The new study involved CNV testing of 2,446 families affected by autism. For comparison, it also included 4,768 individuals unaffected by neurologic or psychiatric disorders.

Overall, CNVs were significantly more common in the participating families who were affected by autism. More importantly, perhaps, the CNV test results provided important medical guidance for many of these families.

For example, in nine of the autism families, CNVs involved a gene that indicates elevated risk for seizures and epilepsy. “This result warrants an immediate referral to a neurologist,” explained Dr. Scherer, senior author on the paper.

CNV testing in the study revealed dozens of genetic changes linked to subtypes of autism associated with other medical issues warranting immediate attention, including risk for muscular dystorphy and syndromes linked with cardiac disorders.

The study added to the growing list of genes linked to the development of autism. According to Autism Speaks, the autism genes identified through CNV testing had surprisingly little overlap with those detected using standard exome gene sequencing. "Yet when the researchers looked at the genes’ function, most affected the same brain pathways as previously discovered genes. 'These gene discoveries will help guide further research on autism subtypes and their treatment'," Dr. Scherer said.

Researchers urge changes in genetic screening to reflect findings
The investigators authoring the new guide urge medical geneticists to add CNV testing to the standard gene tests for autism and to consult medical recommendations for the many autism-linked syndromes that CNV testing can reveal. CNV testing is widely available, though it is not part of standard genetic screening practice for autism in North America.

Whole genome sequencing will be the next step for individualizing diagnosis and treatment of autism, according to Dr. Scherer, though it too, is not yet widely available in medical settings.

"Convergence of Genes and Cellular Pathways Dysregulated in Autism Spectrum Disorders" published online April 24, 2014, was jointly supported through the main funders of the International Autism Genome Project: Autism Speaks, the Health Research Board (Ireland), the Hillbrand Foundations, the Genome Canada, the Ontario Genomics Institute, and the Canadian Institutes of Health Research.