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Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging.
Prenat Diagn. 2020 07; 40(8):972-983.PD

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 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.

Authors+Show Affiliations

Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands.Department of Obstetrics and Gynecology, Radboud University Medical Centre, Nijmegen, The Netherlands.Department of Clinical Genetics, AMsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.Department of Clinical Genetics, AMsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.Department of Clinical Genetics, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.Department of Genetics, Utrecht University Medical Center, Utrecht, The Netherlands.Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.Department of Human Genetics, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

32333414

Citation

Deden, Chantal, et al. "Rapid Whole Exome Sequencing in Pregnancies to Identify the Underlying Genetic Cause in Fetuses With Congenital Anomalies Detected By Ultrasound Imaging." Prenatal Diagnosis, vol. 40, no. 8, 2020, pp. 972-983.
Deden C, Neveling K, Zafeiropopoulou D, et al. Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging. Prenat Diagn. 2020;40(8):972-983.
Deden, C., Neveling, K., Zafeiropopoulou, D., Gilissen, C., Pfundt, R., Rinne, T., de Leeuw, N., Faas, B., Gardeitchik, T., Sallevelt, S. C. E. H., Paulussen, A., Stevens, S. J. C., Sikkel, E., Elting, M. W., van Maarle, M. C., Diderich, K. E. M., Corsten-Janssen, N., Lichtenbelt, K. D., Lachmeijer, G., ... van Zelst-Stams, W. A. G. (2020). Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging. Prenatal Diagnosis, 40(8), 972-983. https://doi.org/10.1002/pd.5717
Deden C, et al. Rapid Whole Exome Sequencing in Pregnancies to Identify the Underlying Genetic Cause in Fetuses With Congenital Anomalies Detected By Ultrasound Imaging. Prenat Diagn. 2020;40(8):972-983. PubMed PMID: 32333414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging. AU - Deden,Chantal, AU - Neveling,Kornelia, AU - Zafeiropopoulou,Dimitra, AU - Gilissen,Christian, AU - Pfundt,Rolph, AU - Rinne,Tuula, AU - de Leeuw,Nicole, AU - Faas,Brigitte, AU - Gardeitchik,Thatjana, AU - Sallevelt,Suzanne C E H, AU - Paulussen,Aimee, AU - Stevens,Servi J C, AU - Sikkel,Esther, AU - Elting,Mariet W, AU - van Maarle,Merel C, AU - Diderich,Karin E M, AU - Corsten-Janssen,Nicole, AU - Lichtenbelt,Klaske D, AU - Lachmeijer,Guus, AU - Vissers,Lisenka E L M, AU - Yntema,Helger G, AU - Nelen,Marcel, AU - Feenstra,Ilse, AU - van Zelst-Stams,Wendy A G, Y1 - 2020/05/05/ PY - 2019/12/23/received PY - 2020/03/01/revised PY - 2020/04/13/accepted PY - 2020/4/26/pubmed PY - 2021/7/14/medline PY - 2020/4/26/entrez SP - 972 EP - 983 JF - Prenatal diagnosis JO - Prenat Diagn VL - 40 IS - 8 N2 - 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 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. SN - 1097-0223 UR - https://www.unboundmedicine.com/medline/citation/32333414/Rapid_whole_exome_sequencing_in_pregnancies_to_identify_the_underlying_genetic_cause_in_fetuses_with_congenital_anomalies_detected_by_ultrasound_imaging_ L2 - https://doi.org/10.1002/pd.5717 DB - PRIME DP - Unbound Medicine ER -