Cell‐based noninvasive prenatal testing (cbNIPT) detects pathogenic copy number variations

Hatt, Lotte; Singh, Ripudaman; Christensen, Rikke; Ravn, Katarina; Christensen, Inga Baasch; Jeppesen, Line Dahl; Nicolaisen, Bolette Hestbek; Kølvraa, Mathias; Schelde, Palle; Andreassen, Lotte Leonore Eivindsdatter; Farlie, Richard; Uldbjerg, Niels; Vogel, Ida

doi:10.1002/ccr3.3211

Cited by 11 publications

(18 citation statements)

References 27 publications

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“…Unfortunately, follow-up confirmation (chromosome analysis or molecular karyotyping) after birth of the female child has not been obtained for this study. The presented case is a part of a larger study that has been running since 2018, where pregnant women in the Central Denmark Region have been offered cbNIPT in addition to cfNIPT albeit in a research setting (Vestergaard et al, 2017 ; Hatt et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Jeppesen

Hatt²,

Singh³

et al. 2021

Front. Genet.

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Background: Cell-free NIPT and cell-based NIPT are risk-free testing options using maternal blood samples to screen for fetal aneuploidies, but the methods differ. For cell-free NIPT, the fetal fraction of cell-free DNA in plasma is analyzed with a high background of maternal DNA. In contrast, for cell-based NIPT, a limited number of the rare, intact fetal cells are isolated for the genetic analysis. This case demonstrates the differences regarding testing for fetal sex-chromosomes anomalies (SCAs) between these two tests.Materials and Methods: A pregnant woman with mosaicism for Turner syndrome opted for NIPT in first trimester. For the cell-free NIPT analysis, DNA extraction, genome-wide massive parallel sequencing, and data analysis were carried out as described by the kit manufacturer (Illumina©, San Diego, CA, USA). For cell-based NIPT, the first sample gave no result, but the woman consented to repeat cell-based NIPT. After whole genome amplification and STR analysis, fetal DNA from three individual fetal cells was subjected to chromosomal microarray (aCGH, Agilent oligoarray, 180 kb).Results: Fetal fraction was 7%, and cell-free NIPT showed 2 copies of chromosomes 13, 18, and 21 and a decreased proportion of chromosome X, suggestive of fetal Turner syndrome. In contrast, the cell-based NIPT result showed no aneuploidy and two X-chromosomes in the fetus.Conclusion: cell-based NIPT may provide a non-invasive testing option to screen for SCAs in women with mosaicism for monosomy-X in blood, where cell-free NIPT cannot discriminate whether the X-loss is maternal or fetal.

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Section: Discussionmentioning

confidence: 99%

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Jeppesen

Hatt²,

Singh³

et al. 2021

Front. Genet.

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“…This eliminates the effect of most maternal confounding factors. With pure fetal DNA, smaller copy number changes down to 1‐2 Mb in size can be detected by CMA or low‐coverage NGS, which is in the range of those commonly identified by CMA on CVS or amniocentesis samples 82–85 . Similar to CMA on invasively obtained samples, cbNIPT currently cannot detect copy‐neutral rearrangements such as balanced translocations or inversions.…”

Section: Cell‐based Nipt Data Analysis Considerationsmentioning

confidence: 99%

Overview and recent developments in cell‐based noninvasive prenatal testing

et al. 2021

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Investigators have long been interested in the natural phenomenon of fetal and placental cell trafficking into the maternal circulation. The scarcity of these circulating cells makes their detection and isolation technically challenging. However, as a DNA source of fetal origin not mixed with maternal DNA, they have the potential of considerable benefit over circulating cell‐free DNA‐based noninvasive prenatal genetic testing (NIPT). Endocervical trophoblasts, which are less rare but more challenging to recover are also being investigated as an approach for cell‐based NIPT. We review published studies from around the world describing both forms of cell‐based NIPT and highlight the different approaches’ advantages and drawbacks. We also offer guidance for developing a sound cell‐based NIPT protocol.

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“…Practically, non-invasive testing should be more manageable compared to invasive testing, as blood sampling is less challenging and time-consuming compared to chorionic villus sampling and amniocentesis. NIPT has been around for 2 decades 23 and has been used clinically for the detection of unbalanced translocations, 24 subchromosomal deletions, 24,25 duplications, 25 copy number variations, 26 and monogenic disorders, 15,[27][28][29] indicating its potential for prenatal testing. Despite the technology being available, implementation of NIPT is challenged by the cost of 30,31 and lack of education of health care professionals on the procedure.…”

Section: Discussionmentioning

confidence: 99%

Patients' choices and opinions on chorionic villous sampling and non‐invasive alternatives for prenatal testing following preimplantation genetic testing for hereditary disorders: A cross‐sectional questionnaire study

et al. 2022

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Objective The aim of this study was to investigate choices of and reasoning behind chorionic villous sampling and opinions on non‐invasive prenatal testing among women and men achieving pregnancy following preimplantation genetic testing (PGT) for hereditary disorders. Methods A questionnaire was electronically submitted to patients who had achieved a clinical pregnancy following PGT at the Center for Preimplantation Genetic Testing, Aalborg University Hospital, Denmark, between 2017 and 2020. Results Chorionic villous sampling was declined by approximately half of the patients. The primary reason for declining was the perceived risk of miscarriage due to the procedure. Nine out of 10 patients responded that they would have opted for a non‐invasive prenatal test if it had been offered. Some patients were not aware that the nuchal translucency scan offered to all pregnant women in the early second trimester only rarely provides information on the hereditary disorder for which PGT was performed. Conclusion Improved counseling on the array of prenatal tests and screenings available might be required to assist patients in making better informed decisions regarding prenatal testing. Non‐invasive prenatal testing is welcomed by the patients and will likely increase the number of patients opting for confirmatory prenatal testing following PGT for hereditary disorders.

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Cell‐based noninvasive prenatal testing (cbNIPT) detects pathogenic copy number variations

Cited by 11 publications

References 27 publications

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Screening for Fetal Aneuploidy and Sex Chromosomal Anomalies in a Pregnant Woman With Mosaicism for Turner Syndrome—Applications and Advantages of Cell-Based NIPT

Overview and recent developments in cell‐based noninvasive prenatal testing

Patients' choices and opinions on chorionic villous sampling and non‐invasive alternatives for prenatal testing following preimplantation genetic testing for hereditary disorders: A cross‐sectional questionnaire study

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