Control of genetic testing for health reasons is substantively different from one country or region to another. However, decreasing costs and consumer demand will almost certainly make whole exome sequencing (WES) and whole genome sequencing (WGS), including direct to consumer testing, a common reality in the near future. A common gatekeeper in all countries for access to the latest tests is cost. Who pays for the tests dramatically alters who holds the power of setting administrative and regulatory thresholds. Thus, introduction of WES and WGS into clinical care is controversial and raises many Ethical, Legal and Social Implications (ELSI).
The least controversial point in healthcare for the introduction of WES is in diagnosis of suspected inherited pediatric disease. With the combined diagnostic cost of current techniques, it seems intuitive that WES should be more efficient. WES can also mitigate the human cost borne by families caused by repetitive negative tests (“diagnostic odyssey”) and gain time in any case for which there is more effective clinical care.
In this issue, Sawyer et al. (Hum Mutat 35:45–49, 2014) used WES as a diagnostic tool for pediatric-onset ataxia, a clinically and genetically heterogeneous group of disorders. No diagnosis had been reached in the 28 families that had previously been tested in standard-of-care molecular investigations for known causes of their disease, prior to inclusion in this study. The WES success rate of 13/28, including 12 autosomal recessive, four simplex cases and nine sib pairs or probands from consanguineous unions, is extraordinarily high. The diagnoses were in 11 known genes and 2 newly identified disease genes where WES enabled transition of diagnostic results to a research setting, increasing the diagnostic yield. In many cases, the unknown phenotypic spectrum of genetic disorders would not have resulted in testing of the appropriate gene, despite the fact that in hindsight, the identified genes explained the patients’ disorders. Most of the patients would not have been diagnosed without WES but had already averaged $7200 CAD in testing with no diagnosis. The authors conservatively conclude that unbiased approaches to genetic testing, such as WES, could be a first-line molecular diagnostic choice for at least some pediatric patients, with potential for cost savings.
There are many voices in the arena of genetic testing (researchers, clinicians, administrators, regulators, funders, families and children) and many opinions on whether, and how, WES should be applied. With the benefit so intuitive for pediatric cases, and as shown through studies like Sawyer et al., WES should be a game changer in clinical and laboratory practice.