Frontiers in Genetics (Mar 2023)

Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool

  • Frédéric Tran Mau-Them,
  • Frédéric Tran Mau-Them,
  • Julian Delanne,
  • Anne-Sophie Denommé-Pichon,
  • Anne-Sophie Denommé-Pichon,
  • Hana Safraou,
  • Hana Safraou,
  • Ange-Line Bruel,
  • Ange-Line Bruel,
  • Antonio Vitobello,
  • Antonio Vitobello,
  • Aurore Garde,
  • Sophie Nambot,
  • Nicolas Bourgon,
  • Caroline Racine,
  • Arthur Sorlin,
  • Arthur Sorlin,
  • Sébastien Moutton,
  • Nathalie Marle,
  • Thierry Rousseau,
  • Paul Sagot,
  • Emmanuel Simon,
  • Catherine Vincent-Delorme,
  • Odile Boute,
  • Cindy Colson,
  • Florence Petit,
  • Marine Legendre,
  • Sophie Naudion,
  • Caroline Rooryck,
  • Clément Prouteau,
  • Estelle Colin,
  • Agnès Guichet,
  • Alban Ziegler,
  • Dominique Bonneau,
  • Godelieve Morel,
  • Mélanie Fradin,
  • Alinoé Lavillaureix,
  • Chloé Quelin,
  • Laurent Pasquier,
  • Sylvie Odent,
  • Gabriella Vera,
  • Alice Goldenberg,
  • Anne-Marie Guerrot,
  • Anne-Claire Brehin,
  • Audrey Putoux,
  • Jocelyne Attia,
  • Carine Abel,
  • Patricia Blanchet,
  • Constance F. Wells,
  • Caroline Deiller,
  • Mathilde Nizon,
  • Mathilde Nizon,
  • Sandra Mercier,
  • Sandra Mercier,
  • Marie Vincent,
  • Marie Vincent,
  • Bertrand Isidor,
  • Bertrand Isidor,
  • Jeanne Amiel,
  • Jeanne Amiel,
  • Rodolphe Dard,
  • Manon Godin,
  • Nicolas Gruchy,
  • Médéric Jeanne,
  • Médéric Jeanne,
  • Elise Schaeffer,
  • Pierre-Yves Maillard,
  • Frédérique Payet,
  • Marie-Line Jacquemont,
  • Christine Francannet,
  • Sabine Sigaudy,
  • Marine Bergot,
  • Marine Bergot,
  • Emilie Tisserant,
  • Marie-Laure Ascencio,
  • Christine Binquet,
  • Yannis Duffourd,
  • Yannis Duffourd,
  • Christophe Philippe,
  • Christophe Philippe,
  • Laurence Faivre,
  • Laurence Faivre,
  • Christel Thauvin-Robinet,
  • Christel Thauvin-Robinet,
  • Christel Thauvin-Robinet

DOI
https://doi.org/10.3389/fgene.2023.1099995
Journal volume & issue
Vol. 14

Abstract

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Introduction: Prenatal ultrasound (US) anomalies are detected in around 5%–10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on the inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following the detection of anomalies on US.Patients and methods: We prospectively performed prenatal trio-ES in 150 fetuses with at least two US anomalies or one US anomaly known to be frequently linked to a genetic disorder. Trio-ES was only performed if the results could influence pregnancy management. Chromosomal microarray (CMA) was performed before or in parallel.Results: A causal diagnosis was identified in 52/150 fetuses (34%) with a median time to diagnosis of 28 days, which rose to 56/150 fetuses (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) fetuses and unfavorable vital and/or neurodevelopmental prognosis was made in 13/56 (24%) fetuses. The overall diagnostic yield was 41% (37/89) with first-line trio-ES versus 31% (19/61) after normal CMA. Trio-ES and CMA were systematically concordant for identification of pathogenic CNV.Conclusion: Trio-ES provided a substantial prenatal diagnostic yield, similar to postnatal diagnosis with a median turnaround of approximately 1 month, supporting its routine implementation during the detection of prenatal US anomalies.

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