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The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies.
Acta Obstet Gynecol Scand. 2021 06; 100(6):1106-1115.AO

Abstract

INTRODUCTION

The aim of this retrospective cohort study was to determine the potential diagnostic yield of prenatal whole exome sequencing in fetuses with structural anomalies on expert ultrasound scans and normal chromosomal microarray results.

MATERIAL AND METHODS

In the period 2013-2016, 391 pregnant women with fetal ultrasound anomalies who received normal chromosomal microarray results, were referred for additional genetic counseling and opted for additional molecular testing pre- and/or postnatally. Most of the couples received only a targeted molecular test and in 159 cases (40.7%) whole exome sequencing (broad gene panels or open exome) was performed. The results of these molecular tests were evaluated retrospectively, regardless of the time of the genetic diagnosis (prenatal or postnatal).

RESULTS

In 76 of 391 fetuses (19.4%, 95% CI 15.8%-23.6%) molecular testing provided a genetic diagnosis with identification of (likely) pathogenic variants. In the majority of cases (91.1%, 73/76) the (likely) pathogenic variant would be detected by prenatal whole exome sequencing analysis.

CONCLUSIONS

Our retrospective cohort study shows that prenatal whole exome sequencing, if offered by a clinical geneticist, in addition to chromosomal microarray, would notably increase the diagnostic yield in fetuses with ultrasound anomalies and would allow early diagnosis of a genetic disorder irrespective of the (incomplete) fetal phenotype.

Authors+Show Affiliations

Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Psychology, Education & Child Studies (DPECS), Erasmus University Rotterdam, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Obstetrics and Prenatal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. Foundation Prenatal Screening Southwest Region of the Netherlands, Rotterdam, The Netherlands.Department of Obstetrics and Prenatal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33249554

Citation

Diderich, Karin E M., et al. "The Potential Diagnostic Yield of Whole Exome Sequencing in Pregnancies Complicated By Fetal Ultrasound Anomalies." Acta Obstetricia Et Gynecologica Scandinavica, vol. 100, no. 6, 2021, pp. 1106-1115.
Diderich KEM, Romijn K, Joosten M, et al. The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies. Acta Obstet Gynecol Scand. 2021;100(6):1106-1115.
Diderich, K. E. M., Romijn, K., Joosten, M., Govaerts, L. C. P., Polak, M., Bruggenwirth, H. T., Wilke, M., van Slegtenhorst, M. A., van Bever, Y., Brooks, A. S., Mancini, G. M. S., van de Laar, I. M. B. H., Kromosoeto, J. N. R., Knapen, M. F. C. M., Go, A. T. J. I., Van Opstal, D., Hoefsloot, L. H., Galjaard, R. H., & Srebniak, M. I. (2021). The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies. Acta Obstetricia Et Gynecologica Scandinavica, 100(6), 1106-1115. https://doi.org/10.1111/aogs.14053
Diderich KEM, et al. The Potential Diagnostic Yield of Whole Exome Sequencing in Pregnancies Complicated By Fetal Ultrasound Anomalies. Acta Obstet Gynecol Scand. 2021;100(6):1106-1115. PubMed PMID: 33249554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The potential diagnostic yield of whole exome sequencing in pregnancies complicated by fetal ultrasound anomalies. AU - Diderich,Karin E M, AU - Romijn,Kathleen, AU - Joosten,Marieke, AU - Govaerts,Lutgarde C P, AU - Polak,Marike, AU - Bruggenwirth,Hennie T, AU - Wilke,Martina, AU - van Slegtenhorst,Marjon A, AU - van Bever,Yolande, AU - Brooks,Alice S, AU - Mancini,Grazia M S, AU - van de Laar,Ingrid M B H, AU - Kromosoeto,Joan N R, AU - Knapen,Maarten F C M, AU - Go,Attie T J I, AU - Van Opstal,Diane, AU - Hoefsloot,Lies H, AU - Galjaard,Robert-Jan H, AU - Srebniak,Malgorzata I, Y1 - 2020/12/28/ PY - 2020/10/30/revised PY - 2020/07/12/received PY - 2020/11/22/accepted PY - 2020/11/30/pubmed PY - 2021/6/29/medline PY - 2020/11/29/entrez KW - diagnostic yield KW - fetal anomalies KW - prenatal diagnosis KW - prenatal whole exome sequencing testing KW - ultrasound anomalies KW - whole exome sequencing SP - 1106 EP - 1115 JF - Acta obstetricia et gynecologica Scandinavica JO - Acta Obstet Gynecol Scand VL - 100 IS - 6 N2 - INTRODUCTION: The aim of this retrospective cohort study was to determine the potential diagnostic yield of prenatal whole exome sequencing in fetuses with structural anomalies on expert ultrasound scans and normal chromosomal microarray results. MATERIAL AND METHODS: In the period 2013-2016, 391 pregnant women with fetal ultrasound anomalies who received normal chromosomal microarray results, were referred for additional genetic counseling and opted for additional molecular testing pre- and/or postnatally. Most of the couples received only a targeted molecular test and in 159 cases (40.7%) whole exome sequencing (broad gene panels or open exome) was performed. The results of these molecular tests were evaluated retrospectively, regardless of the time of the genetic diagnosis (prenatal or postnatal). RESULTS: In 76 of 391 fetuses (19.4%, 95% CI 15.8%-23.6%) molecular testing provided a genetic diagnosis with identification of (likely) pathogenic variants. In the majority of cases (91.1%, 73/76) the (likely) pathogenic variant would be detected by prenatal whole exome sequencing analysis. CONCLUSIONS: Our retrospective cohort study shows that prenatal whole exome sequencing, if offered by a clinical geneticist, in addition to chromosomal microarray, would notably increase the diagnostic yield in fetuses with ultrasound anomalies and would allow early diagnosis of a genetic disorder irrespective of the (incomplete) fetal phenotype. SN - 1600-0412 UR - https://www.unboundmedicine.com/medline/citation/33249554/The_potential_diagnostic_yield_of_whole_exome_sequencing_in_pregnancies_complicated_by_fetal_ultrasound_anomalies_ L2 - https://doi.org/10.1111/aogs.14053 DB - PRIME DP - Unbound Medicine ER -