Singleton exome sequencing of 90 fetuses with ultrasound anomalies revealing novel disease-causing variants and genotype-phenotype correlations.
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:
04 2022
04 2022
Historique:
received:
17
03
2021
accepted:
15
11
2021
revised:
25
10
2021
pubmed:
3
1
2022
medline:
12
4
2022
entrez:
2
1
2022
Statut:
ppublish
Résumé
Exome sequencing has been increasingly implemented in prenatal genetic testing for fetuses with morphological abnormalities but normal rapid aneuploidy detection and microarray analysis. We present a retrospective study of 90 fetuses with different abnormal ultrasound findings, in which we employed the singleton exome sequencing (sES; 75 fetuses) or to a lesser extent (15 fetuses) a multigene panel analysis of 6713 genes as a primary tool for the detection of monogenic diseases. The detection rate of pathogenic or likely pathogenic variants in this study was 34.4%. The highest diagnostic rate of 56% was in fetuses with multiple anomalies, followed by cases with skeletal or renal abnormalities (diagnostic rate of 50%, respectively). We report 20 novel disease-causing variants in different known disease-associated genes and new genotype-phenotype associations for the genes KMT2D, MN1, CDK10, and EXOC3L2. Based on our data, we postulate that sES of fetal index cases with a concurrent sampling of parental probes for targeted testing of the origin of detected fetal variants could be a suitable tool to obtain reliable and rapid prenatal results, particularly in situations where a trio analysis is not possible.
Identifiants
pubmed: 34974531
doi: 10.1038/s41431-021-01012-7
pii: 10.1038/s41431-021-01012-7
pmc: PMC8991249
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
428-438Informations de copyright
© 2021. The Author(s).
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