Chapter 13 - Exome and Genome Sequencing

Abstract

Whole exome sequencing (WES) has been recently integrated into pediatric and adult care to identify suspected single gene disorders. It is beginning to be introduced for prenatal genetic diagnosis for pregnancies with fetal anomalies for which standard testing with chromosomal microarray analysis (CMA) and karyotyping has been unrevealing. Research and early clinical experience with fetal WES indicate that the detection rate of clinically significant sequence variants varies by indication and type of fetal anomalies present but is likely higher than that of CMA. This higher molecular diagnostic rate has significant benefits for prenatal diagnosis but as with CMA, there is an associated risk for detecting variants of uncertain significance and incidental findings unrelated to the fetal phenotype. Although diagnostic fetal WES under guidance by genetics experts can be considered for fetal anomalies, more studies are needed to determine its clinical utility and optimal integration into prenatal diagnosis, and to establish how best to manage variants of uncertain significance and incidental findings.