Diagnostic yield and clinical impact of prenatal whole exome sequencing (WES) – four-year single center experience
Year: 2025
Type: article
Study design: Observational Study
Abstract: Objectives This study evaluates the diagnostic yield of prenatal whole exome sequencing (WES) and its impact on outcome, such as termination of pregnancy (TOP) or neonatal management. Methods A retrospective analysis of more than 4 years of prenatal WES at a single genetic center was performed. Inclusion criteria included normal genome-wide deletion/duplication analysis and ≥1 ultrasound anomaly. Trio analysis was performed, filtering for de novo , compound heterozygous, homozygous, and hemizygous variants, complemented by a genome-wide phenotype-driven analysis. Results (Likely) pathogenic variants fitting the phenotype were identified in 36 of 171 cases (21.1 %), of which 19 were de novo , 14 autosomal recessive, one autosomal dominant, and 2 X-linked dominant. Median turnaround time was 16 days. Parents opted for TOP in 21 cases, three resulted in intrauterine death, 11 were carried to term and one was lost to follow-up. Among the neonates, the diagnosis led to optimized postnatal management in 8/11 (72.7 %), abstinence of care in two (18.2 %) and exclusion of syndromic disorders in one (9.1 %). Conclusions Our findings indicate that in 1/5 pregnancies with ultrasound anomalies and normal deletion/duplication analysis, a (likely) pathogenic variant explaining the phenotype can be identified. The high proportion (17/36 or 47.2 %) of inherited variants highlights the importance of WES for recurrence risk assessment.
Source: Journal of Perinatal Medicine
Institutions: University of Antwerp, Antwerp University Hospital
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4415567499