Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging
Deden, Chantal; Neveling, Kornelia; Zafeiropopoulou, Dimitra; Gilissen, Christian; Pfundt, Rolph; Rinne, Tuula; de Leeuw, Nicole; Faas, Brigitte; Gardeitchik, Thatjana; Sallevelt, Suzanne C E H; Paulussen, Aimee; Stevens, Servi J C; Sikkel, Esther; Elting, Mariet W; van Maarle, Merel C; Diderich, Karin E M; Corsten-Janssen, Nicole; Lichtenbelt, Klaske D; Lachmeijer, Guus; Vissers, Lisenka E L M; Yntema, Helger G; Nelen, Marcel; Feenstra, Ilse; van Zelst-Stams, Wendy A G
(2020) Prenatal Diagnosis, volume 40, issue 8, pp. 972 - 983
(Article)
Abstract
Objective: The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging. Methods: In this observational study, we analyzed the first 54 cases referred to
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our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7). Results: A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases. Conclusions: These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.
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Keywords: Obstetrics and Gynaecology, Genetics(clinical)
ISSN: 0197-3851
Publisher: John Wiley & Sons Inc.
Note: Funding Information: The authors would like to acknowledge all patients and parents who contributed to this study. We thank Saskia van der Crabben (AMU, location VUmc) and Floor Duikers (AMU, location AMC); Yvonne Arens, Christine de Die‐Smulders and Malou Heijligers (MUMC+); Jeske van Harssel, Marije Koopmans and Saskia Hopman (UMCU); and Dominique Smeets, Carlo Marcelis, Sonja de Munnik, Maartje van Rij, Anneke Vulto‐van Silfhout, Marjolein Willemsen and Gwendolyn Woldringh (Radboudumc) for sharing genotypic and phenotypic data. We thank the members of the Genome Technology Center, Department of Human Genetics, Radboud university Medical Center, Nijmegen, for performing rWES library preparation and sequencing. The aim of this study contribute to the Solve‐RD project (to L.E.L.M.V.) which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 779257. This work was financially supported by grants from the Netherlands Organisation for Health Research and Development (ZonMw) (843002608 and 84002003 to L.E.L.M.V. and W.A.G.v. Z.‐S.). Funding Information: The authors would like to acknowledge all patients and parents who contributed to this study. We thank Saskia van der Crabben (AMU, location VUmc) and Floor Duikers (AMU, location AMC); Yvonne Arens, Christine de Die-Smulders and Malou Heijligers (MUMC+); Jeske van Harssel, Marije Koopmans and Saskia Hopman (UMCU); and Dominique Smeets, Carlo Marcelis, Sonja de Munnik, Maartje van Rij, Anneke Vulto-van Silfhout, Marjolein Willemsen and Gwendolyn Woldringh (Radboudumc) for sharing genotypic and phenotypic data. We thank the members of the Genome Technology Center, Department of Human Genetics, Radboud university Medical Center, Nijmegen, for performing rWES library preparation and sequencing. The aim of this study contribute to the Solve-RD project (to L.E.L.M.V.) which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 779257. This work was financially supported by grants from the Netherlands Organisation for Health Research and Development (ZonMw) (843002608 and 84002003 to L.E.L.M.V. and W.A.G.v. Z.-S.). Publisher Copyright: © 2020 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.
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