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
. 2024 Mar;44(3):304-316.
doi: 10.1002/pd.6529. Epub 2024 Feb 27.

Noninvasive single-cell-based prenatal genetic testing: A proof of concept clinical study

Michelle Bellair  1 , Elisabete Amaral  1 , Mason Ouren  1 , Cameron Roark  1 , Jaeweon Kim  1 , April O'Connor  1 , Adrianna Soriano  1 , Margaret L Schindler  1 , Ronald J Wapner  2 , Joanne L Stone  3 , Nicola Tavella  3 , Audrey Merriam  4 , Lauren Perley  4 , Amy M Breman  5 , Arthur L Beaudet  1
Affiliations

Noninvasive single-cell-based prenatal genetic testing: A proof of concept clinical study

Michelle Bellair et al. Prenat Diagn. 2024 Mar.

Abstract

Objective: To clinically assess a cell-based noninvasive prenatal genetic test using sequence-based copy number analysis of single trophoblasts from maternal blood.

Methods: Blood was obtained from 401 (243 + 158) individuals (8-22 weeks) and shipped overnight. Red cells were lysed, and nucleated cells stained for cytokeratin (CK) and CD45 and enriched for positive CK staining. Automated scanning was used to identify and pick single CK+ /CD45- trophoblasts which were subjected to next-generation sequencing.

Results: Blood was obtained from 243 pregnancies scheduled for CVS or amniocentesis. Luna results were normal for 160 singletons while 15 cases were abnormal (14 aneuploidy and one monozygotic twin with Williams syndrome deletion). The deletion was confirmed in both fetuses. Placental mosaicism occurred in 7 of 236 (3.0%) Luna cases and in 3 of 188 (1.6%) CVS cases (total 4.6%). No scorable trophoblasts were recovered in 32 of 236 usable samples. Additionally, 158 low-risk pregnancies not undergoing CVS/amniocentesis showed normal results in 133 cases. Seven had aneuploidy results, and there were three likely pathogenic deletions/duplications, including one15q11-q13 deletion.

Conclusion: Although the sample size is modest and statistically accurate measures of test performance are not possible, the Luna test detected aneuploidy and deletions/duplications based on concordance with CVS/amniocentesis.

PubMed Disclaimer

References

REFERENCES

    1. Salomon LJ, Sotiriadis A, Wulff CB, Odibo A, Akolekar R. Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis. Ultrasound Obstet Gynecol. 2019;54(4):442-451. https://doi.org/10.1002/uog.20353
    1. Walknowska J, Conte FA, Grumbach MM. Practical and theoretical implications of fetal-maternal lymphocyte transfer. Lancet. 1969;1(7606):1119-1122. https://doi.org/10.1016/s0140-6736(69)91642-0
    1. Hatt L, Brinch M, Singh R, et al. A new marker set that identifies fetal cells in maternal circulation with high specificity. Prenat Diagn. 2014;34(11):1066-1072. https://doi.org/10.1002/pd.4429
    1. Hatt L, Brinch M, Singh R, et al. Characterization of fetal cells from the maternal circulation by microarray gene expression analysis--could the extravillous trophoblasts be a target for future cell-based non-invasive prenatal diagnosis? Fetal Diagn Ther. 2014;35(3):218-227. https://doi.org/10.1159/000356073
    1. Navin N, Kendall J, Troge J, et al. Tumour evolution inferred by single-cell sequencing. Nature. 2011;472(7341):90-94. https://doi.org/10.1038/nature09807

Publication types

Grants and funding