Cell-based non-invasive prenatal testing for monogenic disorders: confirmation of unaffected fetuses following preimplantation genetic testing
Toft CLF1,2, Ingerslev HJ3, Kesmodel US2,3, Hatt L4, Singh R4, Ravn K4, Nicolaisen BH4, Christensen IB4, Kølvraa M4, Jeppesen LD4, Schelde P4, Vogel I5, Uldbjeg N6, Farlie R7, Sommer S8, Østergård MLV9, Jensen AN10, Mogensen H11, Kjartansdóttir KR12, Degn B1, Okkels H1, Ernst A1, Pedersen IS1,2.
Journal of Assisted Reproduction and Genetics, 2021, volume 38, pages 1959-1970.
1Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark
2Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
3Fertility Unit, Aalborg University Hospital, Aalborg, Denmark
4ARCEDI Biotech ApS, Vejle, Denmark
5Department of Clinical Genetic, Aarhus University Hospital, Aarhus, Denmark
6Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark
7Department of Obstetrics and Gynecology, Viborg Regional Hospital, Viborg, Denmark
8Department of Obstetrics and Gynecology, Horsens Regional Hospital, Horsens, Denmark
9Department of Obstetrics and Gynecology, Randers Regional Hospital, Randers, Denmark
10Department of Obstetrics and Gynecology, Aalborg University Hospital, Aalborg, Denmark
11Department of Obstetrics and Gynecology, Kolding Regional Hospital, Kolding, Denmark
12Molecular Genetics Laboratory, Department of Clinical Genetics, University Hospital Copenhagen, Copenhagen, Denmark
DOI: 10.1007/s10815-021-02104-5
PMID: 33677749
Abstract:
Purpose:
Proof of concept of the use of cell-based non-invasive prenatal testing (cbNIPT) as an alternative to chorionic villus sampling (CVS) following preimplantation genetic testing for monogenic disorders (PGT-M).
Method:
PGT-M was performed by combined testing of short tandem repeat (STR) markers and direct mutation detection, followed by transfer of an unaffected embryo. Patients who opted for follow-up of PGT-M by CVS had blood sampled, from which potential fetal extravillous throphoblast cells were isolated. The cell origin and mutational status were determined by combined testing of STR markers and direct mutation detection using the same setup as during PGT. The cbNIPT results with respect to the mutational status were compared to those of genetic testing of the CVS.
Results:
Eight patients had blood collected between gestational weeks 10 and 13, from which 33 potential fetal cell samples were isolated. Twenty-seven out of 33 isolated cell samples were successfully tested (82%), of which 24 were of fetal origin (89%). This corresponds to a median of 2.5 successfully tested fetal cell samples per case (range 1–6). All fetal cell samples had a genetic profile identical to that of the transferred embryo confirming a pregnancy with an unaffected fetus, in accordance with the CVS results.
Conclusion:
These findings show that although measures are needed to enhance the test success rate and the number of cells identified, cbNIPT is a promising alternative to CVS.
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Research Coordinator:
Christian Liebst Frisk Toft
Research Coordinator, Post.Doc., Molecular Biologist, Ph.D.
Center for Preimplantation Genetic Testing
Aalborg University Hospital
E-mail: christian.toft@rn.dk
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