Placental Studies Elucidate Discrepancies Between NIPT Showing a Structural Chromosome Aberration and a Differently Abnormal Fetal Karyotype

Overview

Journal Prenat Diagn

Publisher Wiley

Specialty Gynecology & Obstetrics

Date 2019 Jul 20

PMID 31321790

Citations 6

Authors

Diane Van Opstal

Stefanie van Veen

Marieke Joosten

Karin E M Diderich

Lutgarde C P Govaerts

Joke Polak

Nicole van Koetsveld

Marjan Boter

Attie T J I Go

Dimitri N M Papatsonis

Krista Prinsen

Lies H Hoefsloot

Malgorzata I Srebniak

Affiliations

Soon will be listed here.

Abstract

Objective: Placental cytogenetic studies may reveal the origin of discordant noninvasive prenatal testing (NIPT). We performed placental studies to elucidate discordances between NIPT showing a structural chromosome aberration and the fetus having a different chromosome aberration in three cases.

Method: Diagnostic testing with genomic SNP microarray was performed in three cases with NIPT showing a duplication on 4q (case 1), a terminal deletion of 13q (case 2), and a terminal deletion of 15q (case 3). Placental studies involved SNP array analysis of cytotrophoblast and mesenchymal core of chorionic villi of four placental quadrants. Clinical follow-up was performed as well.

Results: Amniotic fluid revealed a different structural chromosome aberration than predicted by NIPT: a terminal 2q deletion (case 1), a segmental uniparental isodisomy of 13q (case 2), and a terminal duplication of 15q and of 13q (case 3). Placental studies revealed the aberration detected with NIPT in the cytotrophoblast, whereas the fetal karyotype was confirmed in the placental mesenchymal core.

Conclusion: Our study shows that targeted cytogenetic investigations for confirmation of NIPT showing a microscopically visible structural chromosome aberration should be avoided, since another aberration, even a submicroscopic one or one involving another chromosome, may be present in the fetus.

Citing Articles

Cell-free placental DNA: What do we really know?.

Yuen N, Lemaire M, Wilson S PLoS Genet. 2024; 20(12):e1011484.

PMID: 39652523 PMC: 11627368. DOI: 10.1371/journal.pgen.1011484.

Single-cell DNA sequencing reveals a high incidence of chromosomal abnormalities in human blastocysts.

Chavli E, Klaasen S, Van Opstal D, Laven J, Kops G, Baart E J Clin Invest. 2024; 134(6).

PMID: 38175717 PMC: 10940095. DOI: 10.1172/JCI174483.

Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: Follow-up results of the TRIDENT-2 study.

van Prooyen Schuurman L, Sistermans E, Van Opstal D, Henneman L, Bekker M, Bax C Am J Hum Genet. 2022; 109(6):1140-1152.

PMID: 35659929 PMC: 9247828. DOI: 10.1016/j.ajhg.2022.04.018.

Cell-free fetal DNA coming in all sizes and shapes.

Chiu R, Lo Y Prenat Diagn. 2021; 41(10):1193-1201.

PMID: 33882153 PMC: 8518878. DOI: 10.1002/pd.5952.

Noninvasive prenatal testing as compared to chorionic villus sampling is more sensitive for the detection of confined placental mosaicism involving the cytotrophoblast.

Van Opstal D, Eggenhuizen G, Joosten M, Diderich K, Govaerts L, Galjaard R Prenat Diagn. 2020; 40(10):1338-1342.

PMID: 32533714 PMC: 7540368. DOI: 10.1002/pd.5766.

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