Mellis, Rhiannon;
Oprych, Kathryn;
Scotchman, Elizabeth;
Hill, Melissa;
Chitty, Lyn S;
(2022)
Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta-analysis.
Prenatal Diagnosis
10.1002/pd.6115.
(In press).
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pES Systematic Review_accepted manuscript.pdf - Accepted Version Access restricted to UCL open access staff until 23 February 2023. Download (2MB) |
Abstract
OBJECTIVES: We conducted a systematic review and meta-analysis to determine the diagnostic yield of ES for prenatal diagnosis of fetal structural anomalies, where karyotype/chromosomal microarray (CMA) is normal. METHODS: Following electronic searches of four databases, we included studies with ≥10 structurally abnormal fetuses undergoing ES or whole genome sequencing (WGS). The incremental diagnostic yield of ES over CMA/karyotype was calculated and pooled in a meta-analysis. Sub-group analyses investigated effects of case selection and fetal phenotype on diagnostic yield. RESULTS: We identified 72 reports from 66 studies, representing 4350 fetuses. The pooled incremental yield of ES was 31% (95% CI 26-36%, p<0.0001). Diagnostic yield was significantly higher for cases pre-selected for likelihood of monogenic aetiology compared to unselected cases (42% vs 15%, p<0.0001). Diagnostic yield differed significantly between phenotypic sub-groups, ranging from 53% (95% CI 42-63%, p<0.0001) for isolated skeletal abnormalities, to 2% (95% CI 0-5%, p = 0.04) for isolated increased nuchal translucency. CONCLUSION: Prenatal ES provides a diagnosis in an additional 31% of structurally abnormal fetuses when CMA/karyotype is non-diagnostic. The expected diagnostic yield depends on the body system(s) affected and can be optimised by pre-selection of cases following multi-disciplinary review to determine that a monogenic cause is likely. This article is protected by copyright. All rights reserved.
| Type: | Article |
|---|---|
| Title: | Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta-analysis. |
| Location: | England |
| DOI: | 10.1002/pd.6115 |
| Publisher version: | https://doi.org/10.1002/pd.6115 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10143965 |
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