Diagnostic Yield of Exome Sequencing Consistent; Targeted Implementation Could Improve True Value

Whole-exome sequencing is permeating clinical practice, particularly for evaluation of pediatric patients with neurological conditions and developmental delay. Two recently published studies show remarkable similarity in the diagnostic yield associated with clinical exome sequencing (CES); however, questions remain regarding the contexts in which the modality would be most cost-effective to implement. While exome-scale sequencing may reduce testing costs, compared to multiple, sequential genetic tests undertaken as part of a diagnostic odyssey, efforts are under way to define the circumstances for which CES will be economically beneficial, clinically useful, and have “personal utility” for patients and their families. “Establishing the mechanism of an individual’s disease has scientific value and satisfies intellectual curiosity, but can also have substantial personal utility for patients and their families,” according to an editorial by Jonathan Berg, M.D., Ph.D., from the University of North Carolina at Chapel Hill, accompanying the two studies in the Oct. 18 issue of theJournal of the American Medical Association. “The personal utility—both positive and negative—afforded by such information, although potentially measurable . . . would be difficult to calculate . . .  in a traditional economic sense. Because these studies focus on the molecular diagnostic yield from a clinical laboratory perspective, the […]