학술논문
Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: A powerful diagnostic tool
Document Type
article
Author
Frédéric Tran Mau-Them; Julian Delanne; Anne-Sophie Denommé-Pichon; Hana Safraou; Ange-Line Bruel; Antonio Vitobello; Aurore Garde; Sophie Nambot; Nicolas Bourgon; Caroline Racine; 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; Sandra Mercier; Marie Vincent; Bertrand Isidor; Jeanne Amiel; Rodolphe Dard; Manon Godin; Nicolas Gruchy; Médéric Jeanne; Elise Schaeffer; Pierre-Yves Maillard; Frédérique Payet; Marie-Line Jacquemont; Christine Francannet; Sabine Sigaudy; Marine Bergot; Emilie Tisserant; Marie-Laure Ascencio; Christine Binquet; Yannis Duffourd; Christophe Philippe; Laurence Faivre; Christel Thauvin-Robinet
Source
Frontiers in Genetics, Vol 14 (2023)
Subject
Language
English
ISSN
1664-8021
Abstract
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.