Prenatal Whole-Genome Sequencing for Fetal Anomalies: Diagnostic Performance, Challenges, and Clinical Implications
Issued Date
2026-04-01
Resource Type
ISSN
16616596
eISSN
14220067
Scopus ID
2-s2.0-105037048027
Journal Title
International Journal of Molecular Sciences
Volume
27
Issue
8
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Molecular Sciences Vol.27 No.8 (2026)
Suggested Citation
Kamlungkuea T., Traisrisilp K., Luewan S., Klangjorhor J., Wattanasirichaigoon D., Tongprasert F. Prenatal Whole-Genome Sequencing for Fetal Anomalies: Diagnostic Performance, Challenges, and Clinical Implications. International Journal of Molecular Sciences Vol.27 No.8 (2026). doi:10.3390/ijms27083568 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116503
Title
Prenatal Whole-Genome Sequencing for Fetal Anomalies: Diagnostic Performance, Challenges, and Clinical Implications
Corresponding Author(s)
Other Contributor(s)
Abstract
Prenatal whole-genome sequencing (WGS) is a comprehensive genetic test for fetal anomalies, enabling simultaneous detection of aneuploidies, copy number variants (CNVs), single-nucleotide variants (SNVs), small insertions/deletions, structural variants, and regions of absence of heterozygosity. However, its clinical performance, optimal sequencing strategies, and implementation challenges remain incompletely defined. We conducted a narrative review of PubMed-indexed studies (1966–December 2025) evaluating prenatal WGS in fetuses with structural anomalies. Across 29 studies, diagnostic yield ranged from approximately 20% to 40%, influenced by phenotype complexity, sequencing depth, and study design. Low-coverage WGS (≤5×) reliably detected large chromosomal abnormalities with a performance comparable to chromosomal microarray analysis. Moderate-coverage WGS (20–40×) additionally enabled detection of SNVs and structural variants, providing up to 30% incremental diagnostic yield after uninformative standard testing. Turnaround times were typically 14–21 days. Higher sequencing depth increases detection of variants of uncertain significance (0.6% to 35.7%) and secondary/incidental findings (1.6–30.8%). Prenatal WGS offers meaningful diagnostic value but requires careful patient selection, multidisciplinary expertise, and structured pre- and post-test genetic counseling to ensure responsible integration into routine clinical practice, with careful consideration of clinical benefit and economic feasibility.