Publication

A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound

Corsten-Janssen, N., Bouman, K., Diphoorn, J. C. D., Scheper, A. J., Kinds, R., El Mecky, J., Breet, H., Verheij, J. B. G. M., Suijkerbuijk, R., Duin, L. K., Manten, G. T. R., van Langen, I. M., Sijmons, R. H., Sikkema-Raddatz, B., Westers, H. & van Diemen, C. C., 20-Jul-2020, In : Prenatal Diagnosis. 24 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Corsten-Janssen, N., Bouman, K., Diphoorn, J. C. D., Scheper, A. J., Kinds, R., El Mecky, J., ... van Diemen, C. C. (2020). A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound. Prenatal Diagnosis. https://doi.org/10.1002/pd.5781

Author

Corsten-Janssen, N ; Bouman, K ; Diphoorn, J C D ; Scheper, A J ; Kinds, R ; El Mecky, J ; Breet, H ; Verheij, J B G M ; Suijkerbuijk, R ; Duin, L K ; Manten, G T R ; van Langen, I M ; Sijmons, R H ; Sikkema-Raddatz, B ; Westers, H ; van Diemen, C C. / A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound. In: Prenatal Diagnosis. 2020.

Harvard

Corsten-Janssen, N, Bouman, K, Diphoorn, JCD, Scheper, AJ, Kinds, R, El Mecky, J, Breet, H, Verheij, JBGM, Suijkerbuijk, R, Duin, LK, Manten, GTR, van Langen, IM, Sijmons, RH, Sikkema-Raddatz, B, Westers, H & van Diemen, CC 2020, 'A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound', Prenatal Diagnosis. https://doi.org/10.1002/pd.5781

Standard

A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound. / Corsten-Janssen, N; Bouman, K; Diphoorn, J C D; Scheper, A J; Kinds, R; El Mecky, J; Breet, H; Verheij, J B G M; Suijkerbuijk, R; Duin, L K; Manten, G T R; van Langen, I M; Sijmons, R H; Sikkema-Raddatz, B; Westers, H; van Diemen, C C.

In: Prenatal Diagnosis, 20.07.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Corsten-Janssen N, Bouman K, Diphoorn JCD, Scheper AJ, Kinds R, El Mecky J et al. A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound. Prenatal Diagnosis. 2020 Jul 20. https://doi.org/10.1002/pd.5781


BibTeX

@article{87334dbfbc3b4511963a66c5ae7aad5c,
title = "A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound",
abstract = "Objective: Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose similar to 40{\%} of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.Methods: We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of similar to 3850 Online Mendelian Inheritance in Man (OMIM) genes.Results: We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35{\%}) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.Conclusion: Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.",
author = "N Corsten-Janssen and K Bouman and Diphoorn, {J C D} and Scheper, {A J} and R Kinds and {El Mecky}, J and H Breet and Verheij, {J B G M} and R Suijkerbuijk and Duin, {L K} and Manten, {G T R} and {van Langen}, {I M} and Sijmons, {R H} and B Sikkema-Raddatz and H Westers and {van Diemen}, {C C}",
note = "This article is protected by copyright. All rights reserved.",
year = "2020",
month = "7",
day = "20",
doi = "10.1002/pd.5781",
language = "English",
journal = "Prenatal Diagnosis",
issn = "0197-3851",
publisher = "Wiley-Blackwell",

}

RIS

TY - JOUR

T1 - A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound

AU - Corsten-Janssen, N

AU - Bouman, K

AU - Diphoorn, J C D

AU - Scheper, A J

AU - Kinds, R

AU - El Mecky, J

AU - Breet, H

AU - Verheij, J B G M

AU - Suijkerbuijk, R

AU - Duin, L K

AU - Manten, G T R

AU - van Langen, I M

AU - Sijmons, R H

AU - Sikkema-Raddatz, B

AU - Westers, H

AU - van Diemen, C C

N1 - This article is protected by copyright. All rights reserved.

PY - 2020/7/20

Y1 - 2020/7/20

N2 - Objective: Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose similar to 40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.Methods: We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of similar to 3850 Online Mendelian Inheritance in Man (OMIM) genes.Results: We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.Conclusion: Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.

AB - Objective: Conventional genetic tests (quantitative fluorescent-PCR [QF-PCR] and single nucleotide polymorphism-array) only diagnose similar to 40% of fetuses showing ultrasound abnormalities. Rapid exome sequencing (rES) may improve this diagnostic yield, but includes challenges such as uncertainties in fetal phenotyping, variant interpretation, incidental unsolicited findings, and rapid turnaround times. In this study, we implemented rES in prenatal care to increase diagnostic yield.Methods: We prospectively studied 55 fetuses. Inclusion criteria were: (a) two or more independent major fetal anomalies, (b) hydrops fetalis or bilateral renal cysts alone, or (c) one major fetal anomaly and a first-degree relative with the same anomaly. In addition to conventional genetic tests, we performed trio rES analysis using a custom virtual gene panel of similar to 3850 Online Mendelian Inheritance in Man (OMIM) genes.Results: We established a genetic rES-based diagnosis in 8 out of 23 fetuses (35%) without QF-PCR or array abnormalities. Diagnoses included MIRAGE (SAMD9), Zellweger (PEX1), Walker-Warburg (POMGNT1), Noonan (PTNP11), Kabuki (KMT2D), and CHARGE (CHD7) syndrome and two cases of Osteogenesis Imperfecta type 2 (COL1A1). In six cases, rES diagnosis aided perinatal management. The median turnaround time was 14 (range 8-20) days.Conclusion: Implementing rES as a routine test in the prenatal setting is challenging but technically feasible, with a promising diagnostic yield and significant clinical relevance.

U2 - 10.1002/pd.5781

DO - 10.1002/pd.5781

M3 - Article

C2 - 32627857

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

SN - 0197-3851

ER -

ID: 128943111