Hands holding puzzle ribbon for autism awareness
Hands holding puzzle ribbon for autism awareness

GeneDx has presented new data supporting exome analysis, and a broader genetic testing approach, for autism spectrum disorders (ASD). This retrospective study is one of the few to examine the genetic basis of ASD and current guidelines around screening and testing. Including almost 19,000 patients, this is among the largest studies to date of genetic testing in ASD.

The study was presented in a poster session at the American Academy of Neurology (AAN) annual virtual meeting this week.

“Use of exome testing as a front-line test will help ensure more patients and clinicians have a more complete diagnosis sooner,” said Paul Kruszka, MD, FACMG., chief medical officer at GeneDx. “The data reinforce that we need to update the standard of care for these patients to choose exome sequencing over panels to provide more children with a diagnosis. We will work tirelessly to help ensure all patients have access to exome, which is a more definitive tool.”

The team evaluated exome analysis for individuals with ASD against current testing methods and uncovered some genes not previously associated with ASD.

They found exome analysis provides higher diagnostic rates of 7.9-21.0% and shorter diagnosis wait times than traditional testing strategies, including Fragile X (FMR1) and array CGH. Though nearly 90% of the 18,911 individuals with ASD who participated in the study had at least one prior negative genetic test, researchers observed a high positive rate of exome analysis, suggesting prior testing contributed to the delay in molecular diagnosis. The results suggest that exome analysis should precede FMR1 and array CGH testing. This finding is also supported by the superior diagnostic yield of exome sequencing over FMR1 and CGH testing found in the medical literature.

In addition, this study revealed a high number of genes not previously connected to autism. Initial analysis identified 1,137 such genes,113 of which were upgraded to disease-causing starting in 2015. Moreover, 60% of genes associated with ASD identified in this study were not found in the Simon Foundation Autism Research Initiative (SFARI) Gene online database—a key resource for the autism research community containing genes implicated in autism susceptibility. This finding further supports the use of exome analysis for the discovery and understanding of genes associated with ASD.

GeneDx offers a clinical genomics program with particular expertise in rare and ultra-rare genetic disorders. In addition to its sequencing service, the company has a suite of additional genetic testing services, including diagnostic testing for hereditary cancers, cardiac, mitochondrial, neurological disorders, prenatal diagnostics, and targeted variant testing

The company’s database of more than 350,000 clinical exomes has been a major driver of discovery in this field. This dataset, supported by annotated and structured clinical information, has made the company a leader in better understanding gene-disease relationships. The company says that today roughly one-quarter of the clinically actionable findings provided to patients come from discoveries first made at GeneDx.

In 2021, the U.S. Centers for Disease Control (CDC) reported approximately 1 in 44 children is diagnosed with autism, and boys are four times more likely to be diagnosed than girls. Most children are diagnosed after age four, although early diagnosis and intervention offers the best opportunities to help support children’s development. Research indicates genetics influence the vast majority of cases.

Also of Interest