Implementation of fetal clinical exome sequencing: Comparing prospective and retrospective cohorts

Martina Marangoni, Guillaume Smits, Gilles Ceysens, Elena Costa, Robert Coulon, Caroline Daelemans, Caroline De Coninck, Sara Derisbourg, Kalina Gajewska, Giulia Garofalo, Caroline Gounongbe, Meriem Guizani, Anne Holoye, Catherine Houba, Jean Makhoul, Christian Norgaard, Cecile Regnard, Stephanie Romée, Jamil Soto, Aurore Stagel-TrabbiaMichel Van Rysselberge, An Vercoutere, Siham Zaytouni, Sarah Bouri, Nicky D'Haene, Dominique D'Onle, Christian Dugauquier, Marie-Lucie Racu, Laureen Rocq, Valérie Segers, Camille Verocq, Ephraim Freddy Avni, Marie Cassart, Anne Massez, Bettina Blaumeiser, Elise Brischoux-Boucher, Saskia Bulk, Thomy De Ravel, Guillaume Debray, Boyan Dimitrov, Sandra Janssens, Kathelijn Keymolen, Marie Laterre, Kim van Berkel, Lionel Van Maldergem, Isabelle Vandernoot, Catheline Vilain, Catherine Donner, Laura Tecco, Dominique Thomas, Julie Désir, Marc Abramowicz, Isabelle Migeotte

Onderzoeksoutput: Articlepeer review

2 Citaten (Scopus)


PURPOSE: We compared the diagnostic yield of fetal clinical exome sequencing (fCES) in prospective and retrospective cohorts of pregnancies presenting with anomalies detected using ultrasound. We evaluated factors that led to a higher diagnostic efficiency, such as phenotypic category, clinical characterization, and variant analysis strategy.

METHODS: fCES was performed for 303 fetuses (183 ongoing and 120 ended pregnancies, in which chromosomal abnormalities had been excluded) using a trio/duo-based approach and a multistep variant analysis strategy.

RESULTS: fCES identified the underlying genetic cause in 13% (24/183) of prospective and 29% (35/120) of retrospective cases. In both cohorts, recessive heterozygous compound genotypes were not rare, and trio and simplex variant analysis strategies were complementary to achieve the highest possible diagnostic rate. Limited prenatal phenotypic information led to interpretation challenges. In 2 prospective cases, in-depth analysis allowed expansion of the spectrum of prenatal presentations for genetic syndromes associated with the SLC17A5 and CHAMP1 genes.

CONCLUSION: fCES is diagnostically efficient in fetuses presenting with cerebral, skeletal, urinary, or multiple anomalies. The comparison between the 2 cohorts highlights the importance of providing detailed phenotypic information for better interpretation and prenatal reporting of genetic variants.

Originele taal-2English
Pagina's (van-tot)344-363
Aantal pagina's20
TijdschriftGenetics in Medicine : Official Journal of the American College of Medical Genetics
Nummer van het tijdschrift2
StatusPublished - feb 2022

Bibliografische nota

Copyright © 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.


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