Implementation of fetal clinical exome sequencing : comparing prospective and retrospective cohorts
| Autor: | Caroline Gounongbe, An Vercoutere, Boyan Dimitrov, Marie Laterre, Ephraim Freddy Avni, Isabelle Vandernoot, Julie Désir, Bettina Blaumeiser, Guillaume Smits, Cecile Regnard, Dominique Thomas, Catherine Donner, Kim Van Berkel, Dominique D'Onle, Lionel Van Maldergem, Laureen Rocq, Jean Makhoul, Catheline Vilain, Martina Marangoni, Jamil Soto, Caroline De Coninck, Giulia Garofalo, Anne Massez, Marie-Lucie Racu, Kathelijn Keymolen, Gilles Ceysens, Robert Coulon, Christian Dugauquier, Caroline Daelemans, Anne Holoye, Marie Cassart, Guillaume Debray, Stephanie Romée, Michel Van Rysselberge, Meriem Guizani, Laura Tecco, Valérie Segers, Thomy De Ravel, Elise Brischoux-Boucher, Sara Derisbourg, Isabelle Migeotte, Catherine Houba, Elena Costa, Siham Zaytouni, Sandra Janssens, Kalina Gajewska, Camille Verocq, Christian Norgaard, Nicky D'Haene, Marc Abramowicz, Saskia Bulk, Aurore Stagel-Trabbia, Sarah Bouri |
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| Přispěvatelé: | Obstetrics, Clinical sciences, Medical Genetics, Mother and Child |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Pediatrics
medicine.medical_specialty Genetic syndromes Chromosomal Proteins Non-Histone Ultrasonography Prenatal Pathology and Forensic Medicine Fetus Pregnancy Prenatal Diagnosis Genotype Obstetrics and Gynaecology Exome Sequencing Medicine Humans Ultrasound abnormalities Genetics(clinical) Exome Genetics (clinical) Exome sequencing Retrospective Studies business.industry Genetic variants Obstetrics and Gynecology General Medicine Fetal clinical exome sequencing Phosphoproteins Female Human medicine business |
| Zdroj: | Genetics in medicine Obstetrical and gynecological survey |
| ISSN: | 1098-3600 0029-7828 |
| Popis: | 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. (C) 2021 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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