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Whole-exome sequencing in fetuses with central nervous system abnormalities

Journal of Perinatology volume 38, pages 1301–1308 (2018)Cite this article

Subjects

Abstract

Objective

We describe our experience with whole-exome sequencing (WES) in fetuses with central nervous system (CNS) abnormalities following a normal chromosomal microarray result.

Methods

During the study period (2014–2017) 7 cases (9 fetuses) with prenatally diagnosed CNS abnormality, whose chromosomal microarray analysis was negative, were offered whole-exome sequencing analysis.

Results

A pathogenic or a likely pathogenic variant was found in 5 cases including a previously described, likely pathogenic de novo TUBA1A variant (Case #1); a previously described homozygous VRK1 variant (Case #2); an X-linked ARX variant (Case #3); a likely pathogenic heterozygous variant in the TUBB3 gene (Case #5). Finally, in two fetuses of the same couple (Case #6), a compound heterozygous state was detected, consisting of the NPHP1 gene deletion and a sequence variant of uncertain significance. Two additional cases had normal WES results.

Conclusion

Whole-exome sequencing may improve prenatal diagnosis in fetuses with CNS abnormalities.

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Author notes

  1. These authors contributed equally: Adi Reches, Liran Hiersch.

Authors and Affiliations

  1. Prenatal Genetic Diagnosis Unit, Genetic Institute, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel

    Adi Reches, Liran Hiersch, Sharon Simchoni, Dalit Barel, Rotem Greenberg & Yuval Yaron

  2. Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel

    Adi Reches, Liran Hiersch, Gustavo Malinger & Yuval Yaron

  3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel

    Adi Reches, Liran Hiersch, Liat Ben Sira, Gustavo Malinger & Yuval Yaron

  4. Radiology Department, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel

    Liat Ben Sira

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  1. Adi Reches
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Correspondence to Liran Hiersch.

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Reches, A., Hiersch, L., Simchoni, S. et al. Whole-exome sequencing in fetuses with central nervous system abnormalities. J Perinatol 38, 1301–1308 (2018). https://doi.org/10.1038/s41372-018-0199-3

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