Exome Sequencing May Aid in Prenatal Diagnosis

Clinical whole-exome sequencing (WES) has been utilized for both pediatric and adult patients with complex, clinical presentations (like developmental disabilities) and typically yields a molecular diagnosis rate of about 30 percent. In these cases clinical WES is effective from both a cost and time perspective in ending long diagnostic odysseys. With shortening turnaround times, experts say that WES will soon be applicable in other patient populations, including critically ill neonates and even prenatally.

Two presentations at the 2016 American College of Medical Genetics and Genomics annual meeting demonstrate the potential for WES to diagnose genetic disorders prenatally, including aneuploidies, large chromosomal deletion and duplication syndromes, as well as single-gene disorders. Timely WES results can inform developmental prognosis, pregnancy management, and recurrence risk for subsequent reproductive planning.

Researchers from Baylor University (Houston) reported results from their first 43 consecutive prenatal cases. The researchers found that the proband WES yielded a diagnosis of 32 percent (11 of 34) versus 33 percent in trio WES (three of nine). The turnaround time (TAT) was dramatically different for the two methods used (average TAT for proband WES of 12 weeks versus one to three weeks for prenatal trio WES). In a second presentation, researchers from GeneDx (Gaithersburg, Md.) shared WES results from 61 fetal samples. Overall, 21 percent (n=13) of cases yielded a definitive molecular diagnosis, 34 percent (n=21) had reportable variants associated with a probable diagnosis, and 30 percent (n=18) tested negative. Similar numbers of cases had one variant (n=20) and two or more variants (n=23) identified.

For more detailed analysis of these reports, see page 1 of the May 2016 issue of Diagnostic Testing & Emerging Technologies.