Comprehensive prenatal diagnostics: Exome versus genome sequencing

Abstract

ObjectiveThis study aimed to assess the diagnostic yield of prenatal genetic testing using trio whole exome sequencing (WES) and trio whole genome sequencing (WGS) in pregnancies with fetal anomalies by comparing the results with conventional chromosomal microarray (CMA) analysis.MethodsA total of 40 pregnancies with fetal anomalies or increased nuchal translucency (NT ≥ 5 mm) were included between the 12th and 21st week of gestation. Trio WES/WGS and CMA were performed in all cases.ResultsThe trio WES/WGS analysis increased the diagnostic yield by 25% in cases with negative CMA results. Furthermore, all six chromosomal aberrations identified by CMA were independently detected by WES/WGS analysis. In total, 16 out of 40 cases obtained a genetic sequence variant, copy number variant, or aneuploidy explaining the phenotype, resulting in an overall WES/WGS diagnostic yield of 40%. WES analysis provided a more reliable identification of mosaic sequence variants than WGS because of its higher sequencing depth.ConclusionsPrenatal WES/WGS proved to be powerful diagnostic tools for fetal anomalies, surpassing the diagnostic yield of CMA. They have the potential to serve as standalone methods for prenatal diagnosis. The study highlighted the limitations of WGS in accurately detecting mosaic variants, which is particularly relevant when analyzing chorionic villus samples.

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“…Some things will certainly change in the future. For example, sonographic evaluation of fetal malformations will increasingly be supplemented by genetic examinations, such as trio-exome sequencing [27,28], in order to better assess the prognosis of anomalies.…”

“…So wird die sonografische fetale Fehlbildungsdiagnostik immer mehr durch genetische Untersuchungen, wie z. B. die Trio-Exom-Sequenzierung [27,28], ergänzt werden, um die Prognose von Anomalien besser einschätzen zu können.…”