Evaluation of the contribution of trio-exome sequencing in selected prenatal indications
Abstract
Objective: This study is an example of the contribution of exome sequencing (ES) in selected prenatal indications, while illustrating the complexity of interpreting prenatal genetic testing. Therefore, one of the aims of this study was to better describe antenatal phenotypes. Methods: This was a multicenter, comparative, prospective study assessing high-throughput sequencing performance (targeted gene panel versus exome sequencing) in selected prenatal indications. Results: Trio-ES was performed on 86 fetuses, allowed making a definite etiological diagnosis in 28% of cases (24/86). One-third of diagnoses were obtained only after exome analysis (8/24, 33%). The diagnostic yield varied according to the indication and was the highest for vermian hypoplasia (5/12, 42%) and polymalformative syndromes (30%, 8/27) indications. The variants identified were mainly missense variants in ciliopathy (18%, 6/33) and cytoskeleton (15%, 5/33) genes. Among the etiological diagnoses, one fetus carried a postzygotic mosaic variant in RHOA. Conclusion: In selected indications, the diagnostic yield of ES was close to 30% and varied according to the indications, showing the importance of clearly define the malformations justifying this approach. An etiological diagnosis was made in 23 families, within a timeframe compatible with pregnancy, thus improving the management of the pregnancy and/or the unborn child.
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BibTeX
@article{chretien2026evaluation,
title = {{Evaluation of the contribution of trio-exome sequencing in selected prenatal indications}},
author = {Manon Chretien and Julien Osouf and Carine Abel and Alexandra Afenjar and Tania Attie-Bitach and Elise Brischoux-Boucher and Lydie Burglen and Nadège Calmels and Nicolas Chassaing and Thomas Courtin and Julian Delanne and Martine Doco-Fenzy and Christèle Dubourg and Benjamin Durand and Salima El Chehadeh and Laurence Faivre and Aurore Garde and Emmanuelle Ginglinger and Virginie Haushalter and Damien Haye and Solveig Heide and Laurence Heidet and Delphine Heron and Clémence Jacquin and Laëtitia Lambert and Jean-Baptiste Lamouche and Vincent Laugel and Antony Le Bechec and Daphné Lehalle and Laurence Michel-Calemard and Edgar Montoya Ramirez and Jean Muller and Sylvie Odent and Olivier Patat and Juliette Piard and Céline Poirsier and Audrey Putoux and Chloé Quelin and Caroline Racine and Nicolas Sananes and Audrey Schalk and Sophie Scheidecker and Christel Thauvin-Robinet and Stéphanie Valence and Anne-Sophie Weingertner and Justine Wourms and Hélène Dollfus and Bénédicte Gerard and Caroline Schluth-Bolard and Elise Schaefer},
journal = {Frontiers in Genetics},
year = {2026},
month = may,
doi = {10.3389/fgene.2026.1761449},
url = {https://univ-rennes.hal.science/hal-05657538v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Evaluation of the contribution of trio-exome sequencing in selected prenatal indications
AU - Manon Chretien
AU - Julien Osouf
AU - Carine Abel
AU - Alexandra Afenjar
AU - Tania Attie-Bitach
AU - Elise Brischoux-Boucher
AU - Lydie Burglen
AU - Nadège Calmels
AU - Nicolas Chassaing
AU - Thomas Courtin
AU - Julian Delanne
AU - Martine Doco-Fenzy
AU - Christèle Dubourg
AU - Benjamin Durand
AU - Salima El Chehadeh
AU - Laurence Faivre
AU - Aurore Garde
AU - Emmanuelle Ginglinger
AU - Virginie Haushalter
AU - Damien Haye
AU - Solveig Heide
AU - Laurence Heidet
AU - Delphine Heron
AU - Clémence Jacquin
AU - Laëtitia Lambert
AU - Jean-Baptiste Lamouche
AU - Vincent Laugel
AU - Antony Le Bechec
AU - Daphné Lehalle
AU - Laurence Michel-Calemard
AU - Edgar Montoya Ramirez
AU - Jean Muller
AU - Sylvie Odent
AU - Olivier Patat
AU - Juliette Piard
AU - Céline Poirsier
AU - Audrey Putoux
AU - Chloé Quelin
AU - Caroline Racine
AU - Nicolas Sananes
AU - Audrey Schalk
AU - Sophie Scheidecker
AU - Christel Thauvin-Robinet
AU - Stéphanie Valence
AU - Anne-Sophie Weingertner
AU - Justine Wourms
AU - Hélène Dollfus
AU - Bénédicte Gerard
AU - Caroline Schluth-Bolard
AU - Elise Schaefer
PY - 2026
DA - 2026/05/11
JO - Frontiers in Genetics
DO - 10.3389/fgene.2026.1761449
UR - https://univ-rennes.hal.science/hal-05657538v1
AB - Objective: This study is an example of the contribution of exome sequencing (ES) in selected prenatal indications, while illustrating the complexity of interpreting prenatal genetic testing. Therefore, one of the aims of this study was to better describe antenatal phenotypes. Methods: This was a multicenter, comparative, prospective study assessing high-throughput sequencing performance (targeted gene panel versus exome sequencing) in selected prenatal indications. Results: Trio-ES was performed on 86 fetuses, allowed making a definite etiological diagnosis in 28% of cases (24/86). One-third of diagnoses were obtained only after exome analysis (8/24, 33%). The diagnostic yield varied according to the indication and was the highest for vermian hypoplasia (5/12, 42%) and polymalformative syndromes (30%, 8/27) indications. The variants identified were mainly missense variants in ciliopathy (18%, 6/33) and cytoskeleton (15%, 5/33) genes. Among the etiological diagnoses, one fetus carried a postzygotic mosaic variant in RHOA. Conclusion: In selected indications, the diagnostic yield of ES was close to 30% and varied according to the indications, showing the importance of clearly define the malformations justifying this approach. An etiological diagnosis was made in 23 families, within a timeframe compatible with pregnancy, thus improving the management of the pregnancy and/or the unborn child.
SN - 1664-8021
ER -