Clinical utility of trio whole exome sequencing in fetuses with ultrasound anomalies

作者：Ziye Zeng, Lan Zhang, Yuqin Zhou, Xue Zhang, Yi Hong, He Li, Yuqi Liu, Jian Li, Qian Chen, Yulin Chen, Guohua Yu, Jing Yi, Yana Zhang, Hua Zhang, Yanling Dong · 发表于：Human Genomics · 年份：2025 · DOI：10.1186/s40246-025-00745-6 · 被引用次数：5 · 研究领域：Prenatal Screening and Diagnostics、Genomics and Rare Diseases、Fetal and Pediatric Neurological Disorders

INTRODUCTION: Ultrasound scanning anomalies in fetuses are a cause for concern and often necessitate further diagnostic procedures. This retrospective study evaluated the utility of trio whole exome sequencing (trio-WES) in the diagnosis of fetuses with ultrasound anomalies. METHODS: We included fetuses diagnosed with fetal ultrasound anomalies referred to the First Affiliated Hospital of Chongqing Medical University between November 2018 and July 2023. Fetal anomalies were classified into structural anomalies, dynamic anomalies, and soft markers. Karyotype analysis, chromosomal microarray analysis (CMA) or copy number variation sequencing (CNV-seq) and trio-WES were performed for the eligible cases. Perinatal outcomes were recorded and evaluated at postnatal follow-up. RESULTS: A total of 316 fetuses were included for the analysis, including 199 (63.0%) cases with structural abnormalities, 63 (19.9%) cases with dynamic abnormalities, and 54 (17.1%) fetuses with ultrasonic soft markers. The diagnostic yield of karyotyping and CMA/CNV-seq was 4.1% (13/316), and Trio-WES achieved an additional diagnosis rate of 15.8% (50/316). Pathogenic or likely pathogenic alleles (P/LP) variants of 132 genes were identified in 125 (39.6%, 125/316) cases, and variant of uncertain significance (VUS) was detected in 81 samples (25.6%, 81/316). Ten cases (3.2%, 10/316,) were found to have pathogenic karyotype or CNVs in supplementary analysis of WES. Fetuses presenting musculoskeletal anomalies ...