Unexpected Finding of Uniparental Disomy Mosaicism in Term Placentas: Is It a Common Feature in Trisomic Placentas?

Overview

Journal Prenat Diagn

Publisher Wiley

Specialty Gynecology & Obstetrics

Date 2018 Sep 7

PMID 30187503

Citations 6

Authors

Diane Van Opstal

Karin E M Diderich

Marieke Joosten

Lutgarde C P Govaerts

Joke Polak

Marjan Boter

Jasper J Saris

Wai Yee Cheung

Stefanie van Veen

Robert van de Helm

Attie T J I Go

Maarten F C M Knapen

Dimitri N M Papatsonis

Anneke Dijkman

Femke de Vries

Robert-Jan H Galjaard

Lies H Hoefsloot

Malgorzata I Srebniak

Affiliations

Soon will be listed here.

Abstract

Objective: Non-invasive prenatal testing (NIPT) detects placental chromosome aberrations. When amniocentesis reveals a normal karyotype, confined placental mosaicism (CPM) may be assumed. In order to confirm this, placental cytogenetic studies were performed.

Method: NIPT was conducted in the course of the Dutch TRIDENT study. Placentas of 10 cases with NIPT results indicating an autosomal trisomy and showing a normal (N = 9) or low mosaic karyotype (N = 1) in amniotic fluid (AF) were investigated. The cytotrophoblast as well as the mesenchymal core of two to four placental chorionic villi biopsies were studied with single nucleotide polymorphism (SNP) array. Clinical outcome data were collected.

Results: In 10/10 cases, CPM was proven. In 3/10 cases trisomy/uniparental disomy (UPD)/biparental disomy (BPD) mosaicism was discovered. In 2/3 cases, all three cell lines were present in the placenta, whereas BPD was found in AF. In 1/3 cases trisomy 22/UPD22 was present in AF while trisomy 22/BPD22 mosaicism was found in the placenta. Five of 10 pregnancies were affected with pre-eclampsia, low birth weight, preterm delivery, and/or congenital malformations.

Conclusion: The presence of trisomy/UPD/BPD mosaicism in 3/10 cases that we investigated proves that trisomic zygote rescue may involve multiple rescue events during early embryogenesis. UPD mosaicism, when present in crucial fetal tissues, may explain the abnormal phenotype in undiagnosed cases.

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References

Fiorentino F, Bono S, Pizzuti F, Duca S, Polverari A, Faieta M . The clinical utility of genome-wide non invasive prenatal screening. Prenat Diagn. 2017; 37(6):593-601. DOI: 10.1002/pd.5053. View

Izumi K, Santani A, Deardorff M, Feret H, Tischler T, Thiel B . Mosaic maternal uniparental disomy of chromosome 15 in Prader-Willi syndrome: utility of genome-wide SNP array. Am J Med Genet A. 2012; 161A(1):166-71. DOI: 10.1002/ajmg.a.35625. View

Henderson K, Shaw T, Barrett I, Telenius A, Wilson R, Kalousek D . Distribution of mosaicism in human placentae. Hum Genet. 1996; 97(5):650-4. DOI: 10.1007/BF02281877. View

Pescia G, Guex N, Iseli C, Brennan L, Osteras M, Xenarios I . Cell-free DNA testing of an extended range of chromosomal anomalies: clinical experience with 6,388 consecutive cases. Genet Med. 2016; 19(2):169-175. PMC: 5303761. DOI: 10.1038/gim.2016.72. View

Wang J, Vaccarello-Cruz M, Ross L, Owen R, Pratt V, Lightman K . Mosaic isochromosome 15q and maternal uniparental isodisomy for chromosome 15 in a patient with morbid obesity and variant PWS-like phenotype. Am J Med Genet A. 2013; 161A(7):1695-701. DOI: 10.1002/ajmg.a.35939. View

Oepkes D, Page-Christiaens G, Bax C, Bekker M, Bilardo C, Boon E . Trial by Dutch laboratories for evaluation of non-invasive prenatal testing. Part I-clinical impact. Prenat Diagn. 2016; 36(12):1083-1090. PMC: 5214231. DOI: 10.1002/pd.4945. View

Kotzot D . Complex and segmental uniparental disomy (UPD): review and lessons from rare chromosomal complements. J Med Genet. 2001; 38(8):497-507. PMC: 1734925. DOI: 10.1136/jmg.38.8.497. View

Bullman H, Lever M, Robinson D, Mackay D, Holder S, Wakeling E . Mosaic maternal uniparental disomy of chromosome 11 in a patient with Silver-Russell syndrome. J Med Genet. 2008; 45(6):396-9. DOI: 10.1136/jmg.2007.057059. View

Van Opstal D, van Maarle M, Lichtenbelt K, Weiss M, Schuring-Blom H, Bhola S . Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study. Genet Med. 2017; 20(5):480-485. PMC: 5929118. DOI: 10.1038/gim.2017.132. View

10.

H A Visser G, Eilers P, Elferink-Stinkens P, Merkus H, Wit J . New Dutch reference curves for birthweight by gestational age. Early Hum Dev. 2009; 85(12):737-44. DOI: 10.1016/j.earlhumdev.2009.09.008. View

11.

Geigl J, Obenauf A, Schwarzbraun T, Speicher M . Defining 'chromosomal instability'. Trends Genet. 2008; 24(2):64-9. DOI: 10.1016/j.tig.2007.11.006. View

12.

Van Opstal D, Diderich K, Joosten M, Govaerts L, Polak J, Boter M . Unexpected finding of uniparental disomy mosaicism in term placentas: Is it a common feature in trisomic placentas?. Prenat Diagn. 2018; 38(12):911-919. PMC: 6282787. DOI: 10.1002/pd.5354. View

13.

Robinson W, Penaherrera M, Jiang R, Avila L, Sloan J, McFadden D . Assessing the role of placental trisomy in preeclampsia and intrauterine growth restriction. Prenat Diagn. 2009; 30(1):1-8. DOI: 10.1002/pd.2409. View

14.

Kotzot D . Complex and segmental uniparental disomy updated. J Med Genet. 2008; 45(9):545-56. DOI: 10.1136/jmg.2008.058016. View

15.

Wolstenholme J, Rooney D, Davison E . Confined placental mosaicism, IUGR, and adverse pregnancy outcome: a controlled retrospective U.K. collaborative survey. Prenat Diagn. 1994; 14(5):345-61. DOI: 10.1002/pd.1970140505. View

16.

Vanneste E, Voet T, Le Caignec C, Ampe M, Konings P, Melotte C . Chromosome instability is common in human cleavage-stage embryos. Nat Med. 2009; 15(5):577-83. DOI: 10.1038/nm.1924. View

17.

Conlin L, Thiel B, Bonnemann C, Medne L, Ernst L, Zackai E . Mechanisms of mosaicism, chimerism and uniparental disomy identified by single nucleotide polymorphism array analysis. Hum Mol Genet. 2010; 19(7):1263-75. PMC: 3146011. DOI: 10.1093/hmg/ddq003. View

18.

Pertile M, Halks-Miller M, Flowers N, Barbacioru C, Kinnings S, Vavrek D . Rare autosomal trisomies, revealed by maternal plasma DNA sequencing, suggest increased risk of feto-placental disease. Sci Transl Med. 2017; 9(405). PMC: 10040211. DOI: 10.1126/scitranslmed.aan1240. View

19.

Eggermann T, Soellner L, Buiting K, Kotzot D . Mosaicism and uniparental disomy in prenatal diagnosis. Trends Mol Med. 2014; 21(2):77-87. DOI: 10.1016/j.molmed.2014.11.010. View

20.

Horsthemke B, Nazlican H, Husing J, Klein-Hitpass L, Claussen U, Michel S . Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader-Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes. Hum Mol Genet. 2003; 12(20):2723-32. DOI: 10.1093/hmg/ddg291. View