Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Chantal Deden; Kornelia Neveling; Dimitra Zafeiropopoulou; Christian Gilissen; Rolph Pfundt; Tuula Rinne; Nicole de Leeuw; Brigitte Faas; Thatjana Gardeitchik; Suzanne C. E. H. Sallevelt; Aimee Paulussen; Servi J. C. Stevens; Esther Sikkel; Mariet W. Elting; Merel C. van Maarle; Karin E. M. Diderich; Nicole Corsten-Janssen; Klaske D. Lichtenbelt; Guus Lachmeijer; Lisenka E. L. M. Vissers; Helger G. Yntema; Marcel Nelen; Ilse Feenstra; Wendy A. G. van Zelst-Stams

doi:10.1002/pd.5717

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

Chantal Deden, Kornelia Neveling, Dimitra Zafeiropopoulou, Christian Gilissen, Rolph Pfundt, Tuula Rinne, Nicole de Leeuw, Brigitte Faas, Thatjana Gardeitchik, Suzanne C. E. H. Sallevelt, Aimee Paulussen, Servi J. C. Stevens, Esther Sikkel, Mariet W. Elting, Merel C. van Maarle, Karin E. M. Diderich, Nicole Corsten-Janssen, Klaske D. Lichtenbelt, Guus Lachmeijer, Lisenka E. L. M. VissersHelger G. Yntema, Marcel Nelen, Ilse Feenstra, Wendy A. G. van Zelst-Stams^*

^*Corresponding author voor dit werk

Onderzoeksoutput: Article › Academic › peer review

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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.

Originele taal-2	English
Pagina's (van-tot)	972-983
Aantal pagina's	12
Tijdschrift	Prenatal Diagnosis
Volume	40
Nummer van het tijdschrift	8
DOI's	https://doi.org/10.1002/pd.5717
Status	Published - jul.-2020

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10.1002/pd.5717Licentie: CC BY

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imagingFinal publisher's version, 995 KBLicentie: CC BY

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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

@article{4919927222e74190b13bd7fa30a9c8ed,

title = "Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging",

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.",

keywords = "DIAGNOSIS, ABNORMALITIES, MICROARRAY, INFANTS, UTILITY",

author = "Chantal Deden and Kornelia Neveling and Dimitra Zafeiropopoulou and Christian Gilissen and Rolph Pfundt and Tuula Rinne and \{de Leeuw\}, Nicole and Brigitte Faas and Thatjana Gardeitchik and Sallevelt, \{Suzanne C. E. H.\} and Aimee Paulussen and Stevens, \{Servi J. C.\} and Esther Sikkel and Elting, \{Mariet W.\} and \{van Maarle\}, \{Merel C.\} and Diderich, \{Karin E. M.\} and Nicole Corsten-Janssen and Lichtenbelt, \{Klaske D.\} and Guus Lachmeijer and Vissers, \{Lisenka E. L. M.\} and Yntema, \{Helger G.\} and Marcel Nelen and Ilse Feenstra and \{van Zelst-Stams\}, \{Wendy A. G.\}",

year = "2020",

month = jul,

doi = "10.1002/pd.5717",

language = "English",

volume = "40",

pages = "972--983",

journal = "Prenatal Diagnosis",

issn = "0197-3851",

publisher = "Wiley-Blackwell",

number = "8",

}

Deden, C, Neveling, K, Zafeiropopoulou, D, Gilissen, C, Pfundt, R, Rinne, T, de Leeuw, N, Faas, B, Gardeitchik, T, Sallevelt, SCEH, Paulussen, A, Stevens, SJC, Sikkel, E, Elting, MW, van Maarle, MC, Diderich, KEM, Corsten-Janssen, N, Lichtenbelt, KD, Lachmeijer, G, Vissers, LELM, Yntema, HG, Nelen, M, Feenstra, I & van Zelst-Stams, WAG 2020, '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, nr. 8, blz. 972-983. https://doi.org/10.1002/pd.5717

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.

PY - 2020/7

Y1 - 2020/7

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.

AB - 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.

KW - DIAGNOSIS

KW - ABNORMALITIES

KW - MICROARRAY

KW - INFANTS

KW - UTILITY

U2 - 10.1002/pd.5717

DO - 10.1002/pd.5717

M3 - Article

SN - 0197-3851

VL - 40

SP - 972

EP - 983

JO - Prenatal Diagnosis

JF - Prenatal Diagnosis

IS - 8

ER -

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging

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