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Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: A systematic review and meta-analysis

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 , 42 (6) pp. 662-685. 10.1002/pd.6115. Green open access

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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
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/pd.6115
Publisher version: https://doi.org/10.1002/pd.6115
Language: English
Additional information: © 2022 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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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