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

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2023.1099995

DOI=10.3389/fgene.2023.1099995

ISSN=1664-8021

ABSTRACT=Introduction: Prenatal ultrasound (US) anomalies are detected in around 5 to 10% of pregnancies. In prenatal diagnosis, exome sequencing (ES) diagnostic yield ranges from 6% to 80% depending on inclusion criteria. We describe the first French national multicenter pilot study aiming to implement ES in prenatal diagnosis following 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 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, rising to 56/150 (37%) after additional investigation. Sporadic occurrences were identified in 34/56 (60%) and unfavorable vital and/or neurodevelopmental prognosis in 13/56 (24%). 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 when US detects prenatal anomalies.