Diagnostic Yield of Exome Sequencing for Pregnancies With and Without Fetal Anomalies and for Stillbirth

作者：Roni Zemet, Christian M. Parobek, April Adams, Mohamad Ali Maktabi, Lena Shay, Linyan Meng, Pengfei Liu, Hongzheng Dai, Fan Xia, Christine M. Eng, Ignatia B. Van den Veyver, Liesbeth Vossaert · 发表于：Prenatal Diagnosis · 年份：2025 · DOI：10.1002/pd.6817 · 被引用次数：2 · 研究领域：Hedgehog Signaling Pathway Studies、Prenatal Screening and Diagnostics、Genomic variations and chromosomal abnormalities

OBJECTIVE: Exome sequencing (ES) benefits the genetic work-up for fetuses with structural anomalies, but data on its utility for fetuses without anomalies and stillbirths is more limited. We report our experience with prenatal ES for all three indications. METHOD: We retrospectively reviewed results from 344 trio-ES performed for fetuses with structural anomalies (N = 262), stillbirths (N = 39), and fetuses without anomalies (N = 43), many of which had a relevant family history. We classified pathogenic variants (P), likely pathogenic variants (LP), or variants of uncertain significance (VUS) favoring pathogenicity in a gene consistent with the fetal phenotype as diagnostic results. We used Fisher's exact test for statistical analysis. RESULTS: Trio-ES provided a diagnosis for 93/262 (35.5%) fetuses with structural anomalies, with comparable yields for multiple and single anomalies (p = 0.81). A molecular diagnosis was made for 10/39 stillbirths (25.6%), of which all but one had structural anomalies, and 66.6% had multiple anomalies. In the absence of structural anomalies, one of 43 fetuses (2.3%) was found to have compound heterozygous pathogenic variants in ORC6 associated with Meier-Gorlin syndrome. CONCLUSION: Prenatal trio-ES yields molecular diagnoses across a spectrum of indications. Larger studies are needed to further define the added benefits and challenges of diagnostic ES for fetuses without anomalies.