(April 24, 2014) Researchers with the Autism Genome Project are calling for the broad use of a relatively new type of genetic test – for copy number variants (CNVs) – as the next step in individualized diagnosis and treatment of autism.
The recommendation is 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. Autism Speaks is the primary funder of the Autism Genome Project, which involves more than 50 research centers in 11 countries.
“With the publication of this study, we should step back to recognize and celebrate the pioneering achievements of the AGP and what they have accomplished in helping to launch the field of genomic risk discovery in autism,” says Autism Speaks Chief Science Officer Rob Ring. “The AGP has generated information that holds the potential to guide medical care for certain individuals with autism today. They have demonstrated that science can work for families, and Autism Speaks is proud to have been a supporter of the work all along the way.”
Autism, CNVs and medical guidance
CNVs are genetic changes that involve duplication or deletion of entire segments of DNA. These segments often span many genes. CNVs have been of particular interest in recent years, with a growing number of studies implicating them as contributing to autism.
However CNVs typically don’t show up on standard genetic tests. 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 just 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,” explains senior author Stephen Scherer of the University of Toronto and The Hospital for Sick Children in Toronto.
Similarly, CNV testing indicated a high risk for muscular dystrophy in several other families affected by autism and identified syndromes associated with heart problems in still others. In all, the CNV testing uncovered dozens of cases where autism-linked gene changes were associated with additional health risks warranting medical attention. (See figure above.)
“This report and its extensive supplements should become a new guidebook for medical geneticists working with families affected by autism,” Dr. Scherer says.
In addition, the study added dozens of genes to the growing list of those that contribute to the development of autism. Surprisingly, the autism genes identified through CNV testing had 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 says.
In conclusion, the investigators 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’s not typically part of standard genetic testing for autism.
Whole genome sequencing will be the next step for individualizing diagnosis and treatment of autism, Dr. Ring adds, though it's not yet available in ordinary medical settings. Autism Speaks has already taken a leadership position in delivering this advanced technology to the autism community with its Autism Ten Thousand Genomes (Aut10K) program.
For a full list of Autism Speaks research grants that supported the Autism Genome Project, click here. Other project supporters include Ireland’s Health Research Board, the United Kingdom’s Medical Research Council, the Hilibrand Foundation, the Genome Canada Ontario Genomics Institute and the Canadian Institutes of Health Research.