Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun;42(7):845-851.
doi: 10.1002/pd.6081. Epub 2021 Dec 27.

Trio exome sequencing is highly relevant in prenatal diagnostics

Heinz Gabriel  1 , Dirk Korinth  1 , Martin Ritthaler  1 , Björn Schulte  1 , Florian Battke  2 , Constantin von Kaisenberg  3 , Max Wüstemann  4 , Bernt Schulze  5 , Almuth Friedrich-Freksa  6 , Lutz Pfeiffer  7 , Michael Entezami  8 , Andreas Schröer  8 , Joachim Bürger  9 , Eva Maria Christina Schwaibold  10 , Holger Lebek  11 , Saskia Biskup  1   2
Affiliations

Trio exome sequencing is highly relevant in prenatal diagnostics

Heinz Gabriel et al. Prenat Diagn. 2022 Jun.

Abstract

Objective: About 3% of newborns show malformations, with about 20% of the affected having genetic causes. Clarification of genetic diseases in postnatal diagnostics was significantly improved with high-throughput sequencing, in particular through whole exome sequencing covering all protein-coding regions. Here, we aim to extend the use of this technology to prenatal diagnostics.

Method: Between 07/2018 and 10/2020, 500 pregnancies with fetal ultrasound abnormalities were analyzed after genetic counseling as part of prenatal diagnostics using WES of the fetus and parents.

Results: Molecular genetic findings could explain ultrasound abnormalities in 38% of affected fetuses. In 47% of these, disease-causing de novo variants were found. Pathogenic variants in genes with autosomal recessive or X-linked inheritance were detected in more than one-third (70/189 = 37%). The latter are associated with increased probability of recurrence, making their detection important for further pregnancies. Average time from sample receipt to report was 12 days in the recent cases.

Conclusion: Trio exome sequencing is a useful addition to prenatal diagnostics due to its high diagnostic yield and short processing time (comparable to chromosome analysis). It covers a wide spectrum of genetic changes. Comprehensive interdisciplinary counseling before and after diagnostics is indispensable.

PubMed Disclaimer

Conflict of interest statement

All authors declare that there is no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Solved cases by type of abnormality detected
FIGURE 2
FIGURE 2
Workflow for variant reporting. Potentially relevant variants are analyzed by a specialized prenatal diagnostic team and assessed with relation to the fetal phenotype. If necessary, external experts (e.g., ultrasound diagnosticians) are consulted
See this image and copyright information in PMC

References

    1. Queißer‐Luft A, Spanger J. Malformations in newborns. Dtsch Arztebl Int. 2006;103(38):2464‐2471.
    1. Jelin AC, Vora N. Whole exome sequencing: applications in prenatal genetics. Obstet Gynecol Clin North Am. 2018;45(1):69‐81. - PMC - PubMed
    1. Saner F, Büchel J, Schönberger H, et al New promising methods of prenatal diagnostics. Gynaecol Pract. 2015;10(7):1‐6.
    1. Shaffer LG, Bui T‐H. The‐Hung B: molecular cytogenetic and rapid aneuploidy detection methods in prenatal diagnosis. Am J Med Genet C Semin Med Genet. 2007;145C(1):87‐98. - PubMed
    1. Callaway JL, Shaffer LG, Chitty LS, Rosenfeld JA, Crolla JA. The clinical utility of microarray technologies applied to prenatal cytogenetics in the presence of a normal conventional karyotype: a review of the literature. Prenat Diagn. 2013;33:1119‐1123. - PMC - PubMed