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. 2023 Aug;43(9):1132-1141.
doi: 10.1002/pd.6402. Epub 2023 Jul 3.

Comprehensive prenatal diagnostics: Exome versus genome sequencing

Ieva Miceikaite  1   2 , Christina Fagerberg  2 , Charlotte Brasch-Andersen  1   2 , Pernille Mathiesen Torring  2 , Britta Schlott Kristiansen  2 , Qin Hao  2 , Lene Sperling  3 , Mette Holm Ibsen  4 , Katrin Löser  5 , Eske Alf Bendsen  6 , Lilian Bomme Ousager  1   2 , Martin Jakob Larsen  1   2
Affiliations

Comprehensive prenatal diagnostics: Exome versus genome sequencing

Ieva Miceikaite et al. Prenat Diagn. 2023 Aug.

Abstract

Objective: This 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.

Methods: A 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.

Results: The 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.

Conclusions: Prenatal 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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References

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