The High Diagnostic Yield of Prenatal Exome Sequencing Followed by 3400 Gene Panel Analysis in 629 Ongoing Pregnancies With Ultrasound Anomalies.

Autor: Diderich KEM; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Bruggenwirth HT; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Joosten M; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Thurik F; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Mijalkovic J; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Polak M; Department of Psychology, Education & Child Studies (DPECS), Erasmus University Rotterdam, Rotterdam, The Netherlands., Kromosoeto J; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Somers-Bolman GM; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., van den Born M; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Drost M; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Galjaard RJH; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Galjaard S; Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands., Hoefsloot LH; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Knapen MFCM; Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands., van Minkelen R; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., van der Schoot V; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., van Slegtenhorst MA; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Sleutels F; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Stuurman KE; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Weerts MJA; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Go ATJI; Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands., Wilke M; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Srebniak MI; Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Prenatal diagnosis [Prenat Diagn] 2024 Nov; Vol. 44 (12), pp. 1444-1450. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1002/pd.6676
Abstrakt: Background: The aim of this study was to evaluate the diagnostic yield of routine exome sequencing (ES) in fetuses with ultrasound anomalies.
Methods: We performed a retrospective analysis of the ES results of 629 fetuses with isolated or multiple anomalies referred in 2019-2022. Variants in a gene panel consisting of approximately 3400 genes associated with multiple congenital anomalies and/or intellectual disability were analyzed. We used trio analysis and filtering for de novo variants, compound heterozygous variants, homozygous variants, X-linked variants, variants in imprinted genes, and known pathogenic variants.
Results: Pathogenic and likely pathogenic variants (class five and four, respectively) were identified in 14.0% (88/629, 95% CI 11.5%-16.9%) of cases. In the current cohort, the probability of detecting a monogenetic disorder was ∼1:7 (88/629, 95% CI 1:8.7-1:5.9), ranging from 1:9 (49/424) in cases with one major anomaly to 1:5 (32/147) in cases with multiple system anomalies.
Conclusions: Our results indicate that a notable number of fetuses (1:7) with ultrasound anomalies and a normal chromosomal microarray have a (likely) pathogenic variant that can be detected through prenatal ES. These results warrant implementation of exome sequencing in selected cases, including those with an isolated anomaly on prenatal ultrasound.
(© 2024 The Author(s). Prenatal Diagnosis published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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