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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 10.1002/pd.6115. (In press).

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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
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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