ASD-associated gene variants may be under-identified by labs

Genetic variants associated with autism spectrum disorder (ASD) may often be missed by commercial laboratory tests, according to a new study.

Omri Bar and colleagues reanalyzed raw DNA sequencing data for 50 individuals with ASD who underwent, along with their parents, whole-genome sequencing (WGS) through an independent healthcare organization using a commercial laboratory. The researchers report, “Our study reveals that high-confidence diagnoses can be assigned to the majority (68%) of individuals with WGS followed by comprehensive reanalysis of raw sequence data.” In contrast, only 28% of cases were identified by WGS alone. The researchers add that half of the genetic variants associated with ASD that they detected were de novo—that is, they arose spontaneously rather than being inherited.

Bar and colleagues conclude that “genetic laboratory reports…are insufficient for eliminating or identifying genetic causes of, and/or contributions to, ASD.” They add, “Since most clinicians are solely reliant on the report generated by genetic laboratories, the implications are that many patients and their families are being insufficiently counseled and genetically investigated concerning important aspects of diagnoses and treatment of ASD.”

The researchers say, “Genetic data obtained were actionable in terms of altering management in the majority of cases. This figure does not include less-tangible benefits such as ending the diagnostic journey, avoiding additional unnecessary testing, and genetic counseling for potential recurrence risks.”

Commenting on the rapid rise in cases of ASD over the past few decades, the researchers note that the human genome changes only slowly over time and speculate that rates of de novo ASD-related gene variants “are accelerating due to some component in our rapidly, and profoundly, changing environment.” They add, “An alternative hypothesis is that [this] rate is relatively static over time, and these variants affect brain homeostasis, but disease may or may not develop dependent on the environment.”

Citations

“Reanalysis of trio whole-genome sequencing data doubles the yield in autism spectrum disorder: De novo variants present in half,” Omri Bar, Elizabeth Vahey, Mark Mintz, Richard E. Frye, and Richard G. Boles, International Journal of Molecular Sciences, January 2024 (free online). Address: Richard Boles, NeurAbilities Healthcare, Voorhees, NJ 08043, [email protected].