ArticleUltrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology2022
Exome sequencing as first-tier test for fetuses with severe central nervous system structural anomalies.
Article in Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.
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Who cites it
42 citing papers in PubMed, 4 syntheses or guidelines pooled 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
- Prenatal Genome-Wide Sequencing analysis (Exome or Genome) in detecting pathogenic Single Nucleotide Variants in fetal Central Nervous System Anomalies: systematic review and meta-analysis.European journal of human genetics : EJHG · 2024Pooled it
- Monogenic conditions and central nervous system anomalies: A prospective study, systematic review and meta-analysis.Prenatal diagnosis · 2024Pooled it
- Molecular Diagnostic Yield of Exome Sequencing in Patients With Congenital Hydrocephalus: A Systematic Review and Meta-Analysis.JAMA network open · 2023Pooled it
- Systematic evaluation of whole exome sequencing for copy number variation detection in prenatal diagnosis.Clinical and translational medicine · 2026Article
- Exome Sequencing in Prenatally Diagnosed Isolated Neural Tube Defects: A Subtype-Specific Analysis.Prenatal diagnosis · 2026Article
- Whole Genome Sequencing in Prenatal Diagnostics: The Danish Approach to Guideline Formation and Implementation Within Public Healthcare.Prenatal diagnosis · 2026Article
- Uncovering the Genetic Landscape of Spinal Dysraphism: A Retrospective Analysis of 150 Fetal Cases.Prenatal diagnosis · 2026Article
- Diagnostic Value of Exome Sequencing in Isolated Polyhydramnios.Prenatal diagnosis · 2026Article
- High Concordance of Copy Number Variants Detected by Chromosomal Microarray and Exome Sequencing in Clinical Diagnostics.Clinical genetics · 2026Article
- Exome Sequencing Resolving a Complex Pediatric Neurodevelopmental Disorder After Inconclusive Prenatal Testing: A Case Report.Children (Basel, Switzerland) · 2026Article
- Contiguous Gene Deletion Involving COL4A1 and COL4A2 in a Patient with Thin Basement Membrane Nephropathy: A Case Report.Nephron · 2026Article
- Utility of prenatal trio whole-exome sequencing and methylation-specific multiplex ligation-dependent probe amplification in the evaluation of fetal growth restriction.Frontiers in medicine · 2026Article
- Fetal Macrocephaly: Prenatal Findings and Follow-Up in Cases With High Risk for Abnormal Outcome.Prenatal diagnosis · 2026Article
- Prenatal Exome Sequencing Analysis in Fetuses With Structural Anomalies: A Multicenter Prospective Cohort Study With Practical Implications.Prenatal diagnosis · 2026Article
- Residual allelic activity likely underlies the low rates of disease expression for predicted loss-of-function variants in population-scale biobanks.American journal of human genetics · 2025Article
- Toward structured fellowships in fetal neuroimaging.Acta obstetricia et gynecologica Scandinavica · 2025Article
- The fetal neurologist: Strategies to improve training, practice, and clinical care.Developmental medicine and child neurology · 2025Review
- Diagnostic Yield of Exome Sequencing for Pregnancies With and Without Fetal Anomalies and for Stillbirth.Prenatal diagnosis · 2025Article
- Current Controversies in Prenatal Diagnosis-Conference Debate 2024: All Fetuses Undergoing Fetal Therapy Should Have Exome Sequencing.Prenatal diagnosis · 2025Review
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13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePrenatally detected central nervous system (CNS) anomalies present a diagnostic challenge. In this study, we compared the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) in fetuses with a major CNS anomaly.
methodsThis was a retrospective study of 114 cases referred for genetic evaluation following termination of pregnancy (TOP) due to a major CNS anomaly detected on prenatal ultrasound. All fetuses were first analyzed by CMA. All CMA-negative cases were offered ES. CMA-positive cases were reanalyzed using ES to assess its ability to detect copy-number variants (CNVs).
resultsCMA identified a pathogenic or likely pathogenic (P/LP) CNV in 11/114 (10%) cases. Eighty-six CMA-negative cases were analyzed using ES, which detected P/LP sequence variants in 38/86 (44%). Among recurrent cases (i.e. cases with a previously affected pregnancy), the incidence of P/LP sequence variants was non-significantly higher compared with non-recurrent ones (12/19 (63%) vs 26/67 (39%); P = 0.06). Among the 38 cases with an ES diagnosis, 20 (53%) were inherited and carried a significant risk of recurrence. Reanalysis of 10 CMA-positive cases by ES demonstrated that the bioinformatics pipeline used for sequence variant analysis also detected all P/LP CNVs, as well as three previously known non-causative CNVs.
conclusionsIn our study, ES provided a high diagnostic yield (> 50%) in fetuses with severe CNS structural anomalies, which may have been partly due to the highly selected case series that included post-TOP cases from a specialist referral center. These data suggest that ES may be considered as a first-tier test for the prenatal diagnosis of major fetal CNS anomalies, detecting both P/LP sequence variants and CNVs. This is of particular importance given the time constraints of an ongoing pregnancy and the risk of recurrence in future pregnancies. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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