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Same performance of exome sequencing before and after fetal autopsy for congenital abnormalities: toward a paradigm shift in prenatal diagnosis?

Abstract

Prenatal exome sequencing could be complex because of limited phenotypical data compared to postnatal/portmortem phenotype in fetuses affected by multiple congenital abnormalities (MCA). Here, we investigated limits of prenatal phenotype for ES interpretation thanks to a blindly reanalysis of postmortem ES data using prenatal data only in fetuses affected by MCA and harboring a (likely)pathogenic variant or a variant of unknown significance (VUS). Prenatal ES identified all causative variant previously reported by postmortem ES (22/24 (92%) and 2/24 (8%) using solo-ES and trio-ES respectively). Prenatal ES identified 5 VUS (in four fetuses). Two of them have been previously reported by postmortem ES. Prenatal ES were negative for four fetuses for which a VUS were diagnosed after autopsy. Our study suggests that prenatal phenotype is not a limitation for implementing pES in the prenatal assessment of unsolved MCA to personalize fetal medicine and could influence indication of postmortem examination.

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Fig. 1: Concordance between prenatal and postmortem ES.

Data availability

The datasets generated and/or analysed during the current study are available from the corresponding author (Pr Christel THAUVIN-ROBINET, mail: christel.thauvin@chu-dijon.fr) on reasonable request.

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Acknowledgements

The authors thank the parents for their participation. The authors also thank cnrgh for exome sequencing, the University of Burgundy Center de Calcul (ccuB) for providing technical support and management of the informatics platform, and the genematcher platform for data sharing.

Funding

This work was funded by the Program Hospitalier de Recherche Clinique (PHRC) Interregional 14-013, the Regional Council of Burgundy and the “Fonds Européen de Développement Régional” (FEDER). Several authors are members of the ERN ITHACA. This study was funded by interregional French Phrc interregional 14-013 FOeTeX.

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Contributions

Conceptualization: CT-R. Data curation: YD. Formal analysis: NB, ML, A-LB, PK, SN, CP, JT, FTM-T, SM, AS, AG, JD, AV. Funding acquisition: JT, CT-R, ML. Writing-original draft: NB. Writing-review and editing: CT-R.

Corresponding author

Correspondence to Christel Thauvin-Robinet.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All fetuses were initially included in this Foetex study, approved by our regional institutional review board and ethics committee (Comité de Protection des Personnes (CPP) EST I (Dijon)). Informed written consent was obtained from all subjects and participating family members.

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Bourgon, N., Garde, A., Bruel, AL. et al. Same performance of exome sequencing before and after fetal autopsy for congenital abnormalities: toward a paradigm shift in prenatal diagnosis?. Eur J Hum Genet (2022). https://doi.org/10.1038/s41431-022-01117-7

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  • DOI: https://doi.org/10.1038/s41431-022-01117-7

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