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Rare autosomal trisomies detected by non-invasive prenatal testing

European Journal of Human Genetics volume 30, pages 1318–1319 (2022)Cite this article

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The Original Article was published on 27 July 2022

In this issue of EJOG, Lannoo et al. [1] present the results of a daunting task; a review of rare autosomal trisomies (RATs) with the goal of providing clinical guidance for women receiving genome-wide (gw) non-invasive prenatal testing (NIPT). RATs are trisomies not involving chromosomes 13, 18, 21, or sex chromosomes. Non-mosaic RATs are seen in a high proportion of first trimester spontaneous abortions. They are only rarely encountered in amniotic fluid cells and exceedingly rare in livebirths where they are only detected in a mosaic state [2]. RATs are surprisingly common in placental cells. To appreciate the challenge in assessing their clinical significance when detected through gwNIPT, it is necessary to briefly summarize current understanding of their origins and the basis for clinical concern.

Early embryos show extensive aneuploidy with strong early selection against abnormal cells. Abnormality may be of meiotic origin or arise in the zygote or in the cell generations shortly thereafter [3]. Only a few cells are destined to become the fetus and therefore the fetus will not necessarily be fully representative of all cells in a mosaic embryo. Moreover, it is likely that lineage-specific cell selection occurs during development and additional somatic cell errors may arise. This view is supported by cytogenetic studies on chorionic villus samples (CVS) where mosaic aneuploidies are occasionally encountered in cytotrophoblasts, or mesenchyme, or both, but are usually not detected in the fetus, i.e., there is a confined placental mosaicism (CPM). Those abnormalities present in both cytotrophoblasts and mesenchyme are more likely to be meiotic in origin and these are more likely to be associated with pregnancy loss [4] or low birth weight [5]. Each specific abnormality is likely to have a different effect on placental development and function. For example, trisomy 16 is associated with a cystic placenta and markedly abnormal maternal serum placenta-derived analytes which are not seen for other trisomies [6]. Further complicating the interpretation of CPM is the need to consider the consequences of uniparental disomy (UPD). Risk for an abnormal phenotype exists when the mosaicism involves a chromosome 6, 7, 11, 14, 15 or 20 due to imprinted genes. The risk for UPD is not the same for each of these chromosomes [1]. There may also be a (currently undefined) risk for abnormality for other chromosomes with UPD because of the expression of a recessive disorder associated with the reduction to homozygosity. Each specific case with placental mosaicism should therefore be viewed as having a distinct, rare, combination of the specific trisomy, the percentage of abnormal cells, cell selection, the compartmentalization of the abnormal cells into different cell lineages, and the consequences of UPD.

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References

  1. Lannoo L, van Straaten K, Breckot J, Brison N, de Catte L, Dimitriadou E, et al. Rare autosomal trisomies detected by non-invasive prenatal testing: an overview of current knowledge. Eur J Hum Genet. 2022. In press.

  2. Benn P. Prenatal diagnosis of chromosome abnormalities through chorionic villus sampling and amniocentesis. 8th ed. Chichester, England: Wiley Blackwell; 2021.

  3. Fragouli E, Munne S, Wells D. The cytogenetic constitution of human blastocysts: insights from comprehensive chromosome screening strategies. Hum Reprod Update. 2019;25:15–33.

    Article  CAS  PubMed  Google Scholar 

  4. Benn P, Grati FR. Aneuploidy in first trimester chorionic villi and spontaneous abortions: windows into the origin and fate of aneuploidy through embryonic and fetal development. Prenat Diagn. 2021;41:519–24.

    Article  CAS  PubMed  Google Scholar 

  5. Toutain J, Goutte-Gattat D, Horovitz J, Saura R. Confined placental mosaicism revisited: impact on pregnancy characteristics and outcome. PloS One. 2018;13:e0195905.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Benn P. Trisomy 16 and trisomy 16 Mosaicism: a review. Am J Med Genet. 1998;79:121–33.

    Article  CAS  PubMed  Google Scholar 

  7. Lo YM. Non-invasive prenatal testing using massively parallel sequencing of maternal plasma DNA: from molecular karyotyping to fetal whole-genome sequencing. Reprod Biomed. Online. 2013;27:593–8.

    Article  CAS  PubMed  Google Scholar 

  8. van Prooyen Schuurman L, Sistermans EA, Van Opstal D, Henneman L, Bekker MN, Bax CJ, et al. Clinical impact of additional findings detected by genome-wide non-invasive prenatal testing: follow-up results of the TRIDENT-2 study. Am J Hum Genet. 2022;109:1344.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Bianchi DW, Chudova D, Sehnert AJ, Bhatt S, Murray K, Prosen TL, et al. Noninvasive prenatal testing and incidental detection of occult maternal malignancies. JAMA. 2015;314:162–9.

    Article  CAS  PubMed  Google Scholar 

  10. Jani JC, Gil MM, Benachi A, Prefumo F, Kagan KO, Tabor A, et al. Genome-wide cfDNA testing of maternal blood. Ultrasound Obstet Gynecol. 2020;55:13–4.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Genetics and Genome Sciences, UConn Health, 263 Farmington Avenue, Farmington, CT, 06032, USA

    Peter Benn

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PB is a consultant and holds stock options in Natera, Inc. He is also on an Advisory Board for Menarini Biomarkers.

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Benn, P. Rare autosomal trisomies detected by non-invasive prenatal testing. Eur J Hum Genet 30, 1318–1319 (2022). https://doi.org/10.1038/s41431-022-01174-y

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