ArticleGenome medicine2022
Application of exome sequencing for prenatal diagnosis of fetal structural anomalies: clinical experience and lessons learned from a cohort of 1618 fetuses.
Article in Genome medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 5 of them syntheses that pooled it.
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45 citing papers in PubMed, 5 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Diagnostic Yield of Sequencing for Prenatal Diagnosis of Fetal Structural Anomalies: An Updated Systematic Review.Prenatal diagnosis · 2026Pooled it
- Is It Feasible to Screen for Fetal De Novo or Paternally Inherited Pathogenic Single Nucleotide Variants in Maternal Plasma Cell-Free DNA? A Systematic Literature Review.Prenatal diagnosis · 2025Pooled it
- Incremental yield of prenatal exome sequencing in fetuses with skeletal system abnormalities: A systematic review and meta-analysis.Acta obstetricia et gynecologica Scandinavica · 2025Pooled it
- Fetal genetic factors in pregnancy loss: Insights from a meta-analysis and effectiveness of whole exome sequencing.PloS one · 2025Pooled it
- A Systematic Review of Methods and Practice for Integrating Maternal, Fetal, and Child Health Outcomes, and Family Spillover Effects into Cost-Utility Analyses.PharmacoEconomics · 2024Pooled it
- Atypical Prenatal Phenotypic Spectrum: A Case Series of Four Unique Presentations With Genetic and Diagnostic Insights.Clinical genetics · 2026Article
- Brachydactyly Type A1 Caused by anReports (MDPI) · 2026Article
- Technological Advances in Molecular Diagnostic Methods for Hereditary Diseases in Preconception and Prenatal Settings.Current issues in molecular biology · 2026Review
- The Asymmetric Threat of Maternal Cell Contamination in Prenatal Single-Gene Testing.Diagnostics (Basel, Switzerland) · 2026Article
- Uncultured Amniocytes Enable Rapid and Clinically Informative Prenatal RNA Sequencing for Genetic Diagnosis.International journal of molecular sciences · 2026Article
- Comparison of Whole Exome Sequencing Commercial Kits Performance Across Diverse Tissue Sources.International journal of molecular sciences · 2026Article
- Evaluating the Utility of RNAseq in Prenatal Diagnostics: Expression Profiles of Cultured Chorionic Villus and Amniotic Fluid Samples.Prenatal diagnosis · 2026Article
- Development and temporal validation of a multimodal post-test risk stratification model for pregnancies with abnormal prenatal findings.Scientific reports · 2026Article
- Whole Genome Sequencing in Prenatal Diagnostics: The Danish Approach to Guideline Formation and Implementation Within Public Healthcare.Prenatal diagnosis · 2026Article
- Inherited variants in autosomal dominant disease genes are a significant cause of fetal structural anomalies.Journal of medical genetics · 2026Article
- Genetic architecture and prognostic significance of suspected fetal microcephaly: evidence from prenatal exome sequencing in a large prospective cohort.Human genomics · 2026Article
- Case Report: A female case of X-linked intellectual disability syndrome type 34 caused by a NONO frameshift variant and literature review.Frontiers in pediatrics · 2026Article
- Article
- Prenatal Exome Sequencing Analysis in Fetuses With Structural Anomalies: A Multicenter Prospective Cohort Study With Practical Implications.Prenatal diagnosis · 2026Article
- Evaluation of the contribution of trio-exome sequencing in selected prenatal indications.Frontiers in genetics · 2026Article
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Authors and funding
30 authors at 4 institutions in 1 country.
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Abstract
backgroundExome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain limited in practice. Herein, we report our experience implementing prenatal ES (pES) in a large cohort of fetuses with anomalies detected by ultrasonography using a hospital-based in-house multidisciplinary team (MDT) facilitated by a three-step genotype-driven followed by phenotype-driven analysis framework.
methodsWe performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. The diagnostic efficiency and its correlation to organ systems involved, phenotypic spectrum, and the clinical impacts of pES results on pregnancy outcomes were analyzed.
resultsA genotype-driven followed by phenotype-driven three-step approach was carried out in all trio pES. Step 1, a genotype-driven analysis resulted in a diagnostic rate of 11.6% (187/1618). Step 2, a phenotype-driven comprehensive analysis yielded additional diagnostic findings for another 28 cases (1.7%; 28/1618). In the final step 3, data reanalyses based on new phenotypes and/or clinical requests found molecular diagnosis in 14 additional cases (0.9%; 14/1618). Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p<0.01). The diagnostic rates were highest in fetuses with skeletal anomalies (30.4%) and multiple organ involvements (25.9%), and lowest in fetuses with chest anomalies (0%). In addition, incidental and secondary findings with childhood-onset disorders were detected in 11 (0.7%) cases. Furthermore, we described the prenatal phenotypes for the first time for 27 gene-associated conditions (20.0%, 27/135) upon a systematic analysis of the diagnosed cases and expanded the phenotype spectrum for 26 (19.3%) genes where limited fetal phenotypic information was available. In the prospective cohort, the combined prenatal ultrasound and pES results had significantly impacted the clinical decisions (61.5%, 648/1053).
conclusionsThe genotype-driven approach could identify about 81.7% positive cases (11.6% of the total cohort) with the initial limited fetal phenotype information considered. The following two steps of phenotype-driven analysis and data reanalyses helped us find the causative variants in an additional 2.6% of the entire cohort (18.3% of all positive findings). Our extensive phenotype analysis on a large number of molecularly confirmed prenatal cases had greatly enriched our current knowledge on fetal phenotype-genotype correlation, which may guide more focused prenatal ultrasound in the future. This is by far the largest pES cohort study that combines a robust trio sequence data analysis, systematic phenotype-genotype correlation, and well-established MDT in a single prenatal clinical setting. This work underlines the value of pES as an essential component in prenatal diagnosis in guiding medical management and parental decision making.
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