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
. 2020 Feb;41(2):432-448.
doi: 10.1002/humu.23935. Epub 2019 Nov 11.

Trio-whole-exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations

Wei Guo  1   2   3 , Yuchen Lai  1   2   3   4 , Zhiqiang Yan  1   2   3   4 , Yuqian Wang  1   2   3 , Yanli Nie  1   2   3 , Shuo Guan  1   2   3 , Ying Kuo  1   2   3 , Wenxin Zhang  1   2   3 , Xiaohui Zhu  1   2   3 , Mei Peng  5 , Xu Zhi  1   2   3 , Yuan Wei  1   2   3 , Liying Yan  1   2   3 , Jie Qiao  1   2   3   4   6
Affiliations

Trio-whole-exome sequencing and preimplantation genetic diagnosis for unexplained recurrent fetal malformations

Wei Guo et al. Hum Mutat. 2020 Feb.

Abstract

Whole-exome sequencing (WES) is widely used to detect genetic mutations that cause Mendelian diseases, and has been successfully applied in combination with preimplantation genetic diagnosis (PGD) to avoid the transmission of genetic defects. We investigated 40 nonconsanguineous families with unexplained, recurrent fetal malformations (two or more malformed fetuses) from May 2016 to December 2018. Using Trio-WES, we identified 32 disease-associated variants in 40 families (80% positive rate), which were subsequently verified. Known Mendelian diseases were identified in 12 families (30%), highly suspected Mendelian diseases in 12 families (30%), variants with uncertain significance in 8 families (20%), and no noticeable variants for 8 families (20%). Further analysis showed variants in 22 genes may cause fetal malformations. Four gene variants were detected in fetuses for the first time, which expanded the spectrum of the disease phenotype. Two novel candidate genes may be related to fetal malformations. Of 26 couples receiving PGD on disease-associated genes, 3 healthy newborns were delivered, and 4 couples are undergoing pregnancies. We reported the fetal data and developed an optimized genetic testing strategy. Our finding strongly suggests the presence of single gene Mendelian disorders in 60% of those families, and PGD services for couples to have healthy babies.

Keywords: Trio-whole-exome sequencing; nonconsanguineous family; preimplantation genetic diagnosis; unexplained recurrent fetal malformations.

PubMed Disclaimer

References

REFERENCES

    1. Abdelrahman, H. A., Al-Shamsi, A. M., Ali, B. R., & Al-Gazali, L. (2018). A null variant in PUS3 confirms its involvement in intellectual disability and further delineates the associated neurodevelopmental disease. Clinical Genetics, 94(6), 586-587. https://doi.org/10.1111/cge.13443
    1. Al-Hamed, M. H., Kurdi, W., Alsahan, N., Alabdullah, Z., Abudraz, R., Tulbah, M., … Albaqumi, M. (2016). Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel. Journal of Medical Genetics, 53(5), 338-347. https://doi.org/10.1136/jmedgenet-2015-103469
    1. Bamshad, M. J., Shendure, J. A., Valle, D., Hamosh, A., Lupski, J. R., Gibbs, R. A., … Nickerson, D. A. (2012). The Centers for Mendelian Genomics: A new large-scale initiative to identify the genes underlying rare Mendelian conditions. American Journal of Medical Genetics, Part A, 158A(7), 1523-1525. https://doi.org/10.1002/ajmg.a.35470
    1. Basel-Vanagaite, L., Hershkovitz, T., Heyman, E., Raspall-Chaure, M., Kakar, N., Smirin-Yosef, P., … Borck, G. (2013). Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum. American Journal of Human Genetics, 93(3), 524-529. https://doi.org/10.1016/j.ajhg.2013.07.005
    1. Bettencourt-Dias, M., Hildebrandt, F., Pellman, D., Woods, G., & Godinho, S. A. (2011). Centrosomes and cilia in human disease. Trends in Genetics, 27(8), 307-315. https://doi.org/10.1016/j.tig.2011.05.004

Publication types

MeSH terms