Discrepancy Between Non-invasive Prenatal Testing Result and Fetal Karyotype Caused by Rare Confined Placental Mosaicism: A Case Report

Overview

Journal World J Clin Cases

Publisher Baishideng Publishing Group

Specialty General Medicine

Date 2022 Sep 26

PMID 36157819

Authors

Zhen Li

Guang-Rui Lai

Affiliations

Soon will be listed here.

Abstract

Background: Confined placental mosaicism (CPM) is one of the major reasons for discrepancies between the results of non-invasive prenatal testing (NIPT) and fetal karyotype analysis.

Case Summary: We encountered a primiparous singleton pregnant woman with a rare CPM consisting of 47,XY,+21; 47,XXY; and 46,XY, who obtained a false-positive result on NIPT with a high risk for trisomy 21. Copy-number variation sequencing on amniotic fluid cells, fetal tissue, and placental biopsies showed that the fetal karyotype was 47,XXY, while the placenta was a rare mosaic of 47,XY,+21; 47,XXY; and 46,XY.

Conclusion: The patient had a rare CPM consisting of 47,XY,+21; 47,XXY; and 46,XY, which caused a discrepancy between the result of NIPT and the actual fetal karyotype. It is important to remember that NIPT is a screening test, not a diagnostic test. Any positive result should be confirmed with invasive testing, and routine ultrasound examination is still necessary after a negative result.

References

DAversa E, Breveglieri G, Pellegatti P, Guerra G, Gambari R, Borgatti M . Non-invasive fetal sex diagnosis in plasma of early weeks pregnants using droplet digital PCR. Mol Med. 2018; 24(1):14. PMC: 6016869. DOI: 10.1186/s10020-018-0016-7. View

Bianchi D, Chudova D, Sehnert A, Bhatt S, Murray K, Prosen T . Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies. JAMA. 2015; 314(2):162-9. DOI: 10.1001/jama.2015.7120. View

Liang D, Lv W, Wang H, Xu L, Liu J, Li H . Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing. Prenat Diagn. 2013; 33(5):409-15. DOI: 10.1002/pd.4033. View

Li J, Xie M, Wang F, Ma J, Li J, Chen C . A rare case of NIPT discrepancy caused by the placental mosaicism of three different karyotypes, 47,XXX, 47,XX,+21, and 48,XXX,+21. Mol Genet Genomic Med. 2020; 8(8):e1279. PMC: 7434741. DOI: 10.1002/mgg3.1279. View

Canick J, Palomaki G, Kloza E, Lambert-Messerlian G, Haddow J . The impact of maternal plasma DNA fetal fraction on next generation sequencing tests for common fetal aneuploidies. Prenat Diagn. 2013; 33(7):667-74. DOI: 10.1002/pd.4126. View

Suzumori N, Sekizawa A, Takeda E, Samura O, Sasaki A, Akaishi R . Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13. Eur J Obstet Gynecol Reprod Biol. 2020; 256:75-81. DOI: 10.1016/j.ejogrb.2020.10.050. View

Faas B, de Ligt J, Janssen I, Eggink A, Wijnberger L, van Vugt J . Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells. Expert Opin Biol Ther. 2012; 12 Suppl 1:S19-26. DOI: 10.1517/14712598.2012.670632. View

Mardy A, Wapner R . Confined placental mosaicism and its impact on confirmation of NIPT results. Am J Med Genet C Semin Med Genet. 2016; 172(2):118-22. DOI: 10.1002/ajmg.c.31505. View

Hayata K, Hiramatsu Y, Masuyama H, Eto E, Mitsui T, Tamada S . Discrepancy between Non-invasive Prenatal Genetic Testing (NIPT) and Amniotic Chromosomal Test due to Placental Mosaicism: A Case Report and Literature Review. Acta Med Okayama. 2017; 71(2):181-185. DOI: 10.18926/AMO/54988. View

10.

Cui W, Liu X, Zhang Y, Wang Y, Chu G, He R . Evaluation of non-invasive prenatal testing to detect chromosomal aberrations in a Chinese cohort. J Cell Mol Med. 2019; 23(11):7873-7878. PMC: 6815821. DOI: 10.1111/jcmm.14614. View

11.

Liang D, Cram D, Tan H, Linpeng S, Liu Y, Sun H . Clinical utility of noninvasive prenatal screening for expanded chromosome disease syndromes. Genet Med. 2019; 21(9):1998-2006. DOI: 10.1038/s41436-019-0467-4. View

12.

West J, Everett C . Preimplantation chromosomal mosaics, chimaeras and confined placental mosaicism. Reprod Fertil. 2022; 3(2):R66-R90. PMC: 9066951. DOI: 10.1530/RAF-21-0095. View

13.

Shaw J, Scotchman E, Chandler N, Chitty L . PREIMPLANTATION GENETIC TESTING: Non-invasive prenatal testing for aneuploidy, copy-number variants and single-gene disorders. Reproduction. 2020; 160(5):A1-A11. DOI: 10.1530/REP-19-0591. View

14.

Lo Y, Chan K, Sun H, Chen E, Jiang P, Lun F . Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med. 2010; 2(61):61ra91. DOI: 10.1126/scitranslmed.3001720. View

15.

Lo Y, Zhang J, Leung T, Lau T, Chang A, Hjelm N . Rapid clearance of fetal DNA from maternal plasma. Am J Hum Genet. 1999; 64(1):218-24. PMC: 1377720. DOI: 10.1086/302205. View

16.

Toutain J, Goutte-Gattat D, Horovitz J, Saura R . Confined placental mosaicism revisited: Impact on pregnancy characteristics and outcome. PLoS One. 2018; 13(4):e0195905. PMC: 5897023. DOI: 10.1371/journal.pone.0195905. View

17.

Curnow K, Wilkins-Haug L, Ryan A, Kirkizlar E, Stosic M, Hall M . Detection of triploid, molar, and vanishing twin pregnancies by a single-nucleotide polymorphism-based noninvasive prenatal test. Am J Obstet Gynecol. 2014; 212(1):79.e1-9. DOI: 10.1016/j.ajog.2014.10.012. View

18.

Tjoa M, Cindrova-Davies T, Spasic-Boskovic O, Bianchi D, Burton G . Trophoblastic oxidative stress and the release of cell-free feto-placental DNA. Am J Pathol. 2006; 169(2):400-4. PMC: 1698796. DOI: 10.2353/ajpath.2006.060161. View

19.

Canick J . Prenatal screening for trisomy 21: recent advances and guidelines. Clin Chem Lab Med. 2011; 50(6):1003-8. DOI: 10.1515/CCLM.2011.671. View

20.

Petersen A, Cheung S, Smith J, Bi W, Ward P, Peacock S . Positive predictive value estimates for cell-free noninvasive prenatal screening from data of a large referral genetic diagnostic laboratory. Am J Obstet Gynecol. 2017; 217(6):691.e1-691.e6. DOI: 10.1016/j.ajog.2017.10.005. View