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=14
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%–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.