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
. 2021 Apr 9:12:616392.
doi: 10.3389/fgene.2021.616392. eCollection 2021.

Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis

Xinyao Zhou  1 , Jia Zhou  1 , Xing Wei  1 , Ruen Yao  2 , Yingjun Yang  1 , Linbei Deng  1 , Gang Zou  1 , Xietong Wang  3 , Yaping Yang  4   5 , Tao Duan  1 , Jian Wang  2 , Luming Sun  1
Affiliations

Value of Exome Sequencing in Diagnosis and Management of Recurrent Non-immune Hydrops Fetalis: A Retrospective Analysis

Xinyao Zhou et al. Front Genet. .

Abstract

The purpose of the study was to use exome sequencing (ES) to study the contribution of single-gene disorders to recurrent non-immune hydrops fetalis (NIHF) and retrospectively evaluate the value of genetic diagnosis on prenatal management and pregnancy outcome. From January 2012 to October 2018, a cohort of 28 fetuses with recurrent NIHF was analyzed by trio ES. Fetuses with immune hydrops, non-genetic factors (including infection, etc.), karyotype, or CNV abnormalities were excluded. Variants were interpreted based on ACMG/AMP guidelines. Fetal therapy was performed on seven fetuses. Of the 28 fetuses, 10 (36%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in eight genes (GBA, GUSB, GBE1, RAPSN, FOXC2, PIEZO1, LZTR1, and FOXP3). Five (18%) fetuses had variant(s) of uncertain significance (VUS). Of the 10 fetuses with definitive molecular diagnosis, five (50%) were diagnosed with inborn errors of metabolism. Among the seven fetuses who received fetal therapy, two had definitive molecular diagnosis and resulted in neonatal death. Among the remaining five fetuses with negative results, four had newborn survival and one had intrauterine fetal death. Trio ES could facilitate genetic diagnosis of recurrent NIHF and improve the prenatal management and pregnancy outcome.

Keywords: exome sequencing; non-immune hydrops fetalis NIHF; prenatal diagnose; prenatal management; single gene disorders.

PubMed Disclaimer

Conflict of interest statement

YaY was employed by the company AiLife Diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The flow diagram of the cohort and outcomes.
See this image and copyright information in PMC

References

    1. Bellini C., Donarini G., Paladini D., Calevo M. G., Bellini T., Ramenghi L. A., et al. (2015). Etiology of non-immune hydrops fetalis: an update. Am. J. Med. Genet. A 167A 1082–1088. 10.1002/ajmg.a.36988 - DOI - PubMed
    1. Bruwer Z., Al Riyami N., Al Dughaishi T., Al Murshedi F., Al Sayegh A., Al Kindy A., et al. (2018). Inborn errors of metabolism in a cohort of pregnancies with non-immune hydrops fetalis: a single center experience. J. Perinat. Med. 46 968–974. 10.1515/jpm-2017-0124 - DOI - PubMed
    1. Burin M. G., Scholz A. P., Gus R., Sanseverino M. T., Fritsh A., Magalhaes J. A., et al. (2004). Investigation of lysosomal storage diseases in nonimmune hydrops fetalis. Prenat. Diagn. 24 653–657. 10.1002/pd.967 - DOI - PubMed
    1. Datkhaeva I., Arboleda V. A., Senaratne T. N., Nikpour G., Meyerson C., Geng Y., et al. (2018). Identification of novel PIEZO1 variants using prenatal exome sequencing and correlation to ultrasound and autopsy findings of recurrent hydrops fetalis. Am. J. Med. Genet. A 176 2829–2834. 10.1002/ajmg.a.40533 - DOI - PubMed
    1. Fotiou E., Martin-Almedina S., Simpson M. A., Lin S., Gordon K., Brice G., et al. (2015). Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat. Commun. 6:8085. 10.1038/ncomms9085 - DOI - PMC - PubMed