Diagnostic yield of whole exome data in fetuses aborted for conotruncal malformations.
Journal
Prenatal diagnosis
ISSN: 1097-0223
Titre abrégé: Prenat Diagn
Pays: England
ID NLM: 8106540
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
revised:
01
04
2022
received:
13
10
2021
accepted:
07
04
2022
pubmed:
15
4
2022
medline:
22
6
2022
entrez:
14
4
2022
Statut:
ppublish
Résumé
We investigated a custom congenital heart disease (CHD) geneset to assess the diagnostic value of whole-exome sequencing (WES) in karyotype- and copy number variation (CNV)-negative aborted fetuses with conotruncal defects (CTDs), and to explore the impact of postnatal phenotyping on genetic diagnosis. We sequentially analyzed CNV-seq and WES data from 47 CTD fetuses detected by prenatal ultrasonography. Fetuses with either a confirmed aneuploidy or pathogenic CNV were excluded from the WES analyses, which were performed following the American College of Medical Genetics and Genomics recommendations and a custom CHD-geneset. Imaging and autopsy were applied to obtain postnatal phenotypic information about aborted fetuses. CNV-seq identified aneuploidy in 7/47 cases while 13/47 fetuses were CNV-positive. Eighty-five rare deleterious variants in 61 genes (from custom geneset) were identified by WES in the remaining 27 fetuses. Of these, five pathogenic or likely pathogenic variants (PV/LPV) were identified in five fetuses, revealing a 10.6% (5/47) incremental diagnostic yield. Furthermore, RERE:c.2461_2472delGGGATGTGGCGA was reclassified as LPV based on postnatal phenotypic data. We have developed and defined a CHD gene panel that can be utilized in a subset of fetuses with CTDs. We demonstrate the utility of incorporating both prenatal and postnatal phenotypic information may facilitate WES diagnostics.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
852-861Informations de copyright
© 2022 John Wiley & Sons Ltd.
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