Exome sequencing for structurally normal fetuses-yields and ethical issues.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
received:
10
01
2022
accepted:
26
07
2022
revised:
01
06
2022
pmc-release:
01
02
2024
pubmed:
8
9
2022
medline:
10
2
2023
entrez:
7
9
2022
Statut:
ppublish
Résumé
The yield of chromosomal microarray analysis (CMA) is well established in structurally normal fetuses (0.4-1.4%). We aimed to determine the incremental yield of exome sequencing (ES) in this population. From February 2017 to April 2022, 1,526 fetuses were subjected to ES; 482 of them were structurally normal (31.6%). Only pathogenic and likely pathogenic (P/LP) variants, per the American College of Medical Genetics and Genomics (ACMG) classification, were reported. Additionally, ACMG secondary findings relevant to childhood were reported. Four fetuses (4/482; 0.8%) had P/LP variants indicating a moderate to severe disease in ATP7B, NR2E3, SPRED1 and FGFR3, causing Wilson disease, Enhanced S-cone syndrome, Legius and Muenke syndromes, respectively. Two fetuses had secondary findings, in RET and DSP. Our data suggest that offering only CMA for structurally normal fetuses may provide false reassurance. Prenatal ES mandates restrictive analysis and careful management combined with pre and post-test genetic counseling.
Identifiants
pubmed: 36071243
doi: 10.1038/s41431-022-01169-9
pii: 10.1038/s41431-022-01169-9
pmc: PMC9905544
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
164-168Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.
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