Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls
Introduction: Circulating fetal cells isolated from maternal blood can be used for prenatal testing, representing a safe alternative to invasive testing. The present study investigated the potential of cell-based noninvasive prenatal testing (NIPT) for diagnosing monogenic disorders dependent on the...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1188472/full |
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| author | Line Dahl Jeppesen Line Dahl Jeppesen Lotte Hatt Ripudaman Singh Palle Schelde Katarina Ravn Christian Liebst Toft Christian Liebst Toft Maria Bach Laursen Jakob Hedegaard Inga Baasch Christensen Bolette Hestbek Nicolaisen Lotte Andreasen Lars Henning Pedersen Lars Henning Pedersen Lars Henning Pedersen Ida Vogel Ida Vogel Dorte Launholt Lildballe Dorte Launholt Lildballe |
| author_facet | Line Dahl Jeppesen Line Dahl Jeppesen Lotte Hatt Ripudaman Singh Palle Schelde Katarina Ravn Christian Liebst Toft Christian Liebst Toft Maria Bach Laursen Jakob Hedegaard Inga Baasch Christensen Bolette Hestbek Nicolaisen Lotte Andreasen Lars Henning Pedersen Lars Henning Pedersen Lars Henning Pedersen Ida Vogel Ida Vogel Dorte Launholt Lildballe Dorte Launholt Lildballe |
| author_sort | Line Dahl Jeppesen |
| collection | DOAJ |
| description | Introduction: Circulating fetal cells isolated from maternal blood can be used for prenatal testing, representing a safe alternative to invasive testing. The present study investigated the potential of cell-based noninvasive prenatal testing (NIPT) for diagnosing monogenic disorders dependent on the mode of inheritance.Methods: Maternal blood samples were collected from women opting for prenatal diagnostics for specific monogenic disorders (N = 7). Fetal trophoblasts were enriched and stained using magnetic activated cell sorting and isolated by fluorescens activated single-cell sorting. Individual cells were subject to whole genome amplification, and cells of fetal origin were identified by DNA-profiling using short tandem repeat markers. The amplified fetal DNA was input for genetic testing for autosomal dominant-, autosomal recessive-, X-linked and repeat expansion disorders by direct variant analysis and haplotyping. The cell-based NIPT results were compared with those of invasive testing.Results: In two cases at risk of skeletal dysplasia, caused by variants in the FGFR3 gene (autosomal dominant disorders), cell-based NIPT correctly stated an affected fetus, but allelic dropout of the normal alleles were observed in both cases. Cell-based NIPT gave an accurate result in two cases at risk of autosomal recessive disorders, where the parents carried either different diastrophic dysplasia causing variants in the SLC26A2 gene or the same cystic fibrosis disease-causing variant in the CFTR gene. Cell-based NIPT accurately identified an affected male fetus in a pregnancy at risk of Duchenne muscular dystrophy (DMD gene, X-linked recessive disorders). In two cases at risk of the myotonic dystrophy type 1 (DMPK gene, repeat expansion disorder), cell-based NIPT correctly detected an affected and an unaffected fetus, respectively.Discussion: Circulating fetal cells can be used to detect both maternally- and paternally inherited monogenic disorders irrespective of the type of variant, however, the risk of allelic dropout must be considered. We conclude that the clinical interpretation of the cell-based NIPT result thus varies depending on the disorders’ mode of inheritance. |
| first_indexed | 2024-03-11T21:28:29Z |
| format | Article |
| id | doaj.art-1de434c9e29148f39b2d71fd2aed3f72 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-03-11T21:28:29Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-1de434c9e29148f39b2d71fd2aed3f722023-09-27T14:04:32ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-09-011410.3389/fgene.2023.11884721188472Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfallsLine Dahl Jeppesen0Line Dahl Jeppesen1Lotte Hatt2Ripudaman Singh3Palle Schelde4Katarina Ravn5Christian Liebst Toft6Christian Liebst Toft7Maria Bach Laursen8Jakob Hedegaard9Inga Baasch Christensen10Bolette Hestbek Nicolaisen11Lotte Andreasen12Lars Henning Pedersen13Lars Henning Pedersen14Lars Henning Pedersen15Ida Vogel16Ida Vogel17Dorte Launholt Lildballe18Dorte Launholt Lildballe19ARCEDI Biotech, Vejle, DenmarkCenter for Fetal Diagnostics, Aarhus University, Aarhus, DenmarkARCEDI Biotech, Vejle, DenmarkARCEDI Biotech, Vejle, DenmarkARCEDI Biotech, Vejle, DenmarkARCEDI Biotech, Vejle, DenmarkDepartment of Molecular Diagnostics, Aalborg University Hospital, Aalborg, DenmarkCenter for Preimplantation Genetic Testing, Aalborg University Hospital, Aalborg, DenmarkARCEDI Biotech, Vejle, DenmarkARCEDI Biotech, Vejle, DenmarkARCEDI Biotech, Vejle, DenmarkARCEDI Biotech, Vejle, DenmarkDepartment of Clinical Genetics, Aarhus University Hospital, Aarhus, DenmarkDepartment of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, DenmarkDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkDepartment of Biomedicine, Aarhus University, Aarhus, DenmarkCenter for Fetal Diagnostics, Aarhus University, Aarhus, DenmarkDepartment of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, DenmarkCenter for Fetal Diagnostics, Aarhus University, Aarhus, DenmarkDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus, DenmarkIntroduction: Circulating fetal cells isolated from maternal blood can be used for prenatal testing, representing a safe alternative to invasive testing. The present study investigated the potential of cell-based noninvasive prenatal testing (NIPT) for diagnosing monogenic disorders dependent on the mode of inheritance.Methods: Maternal blood samples were collected from women opting for prenatal diagnostics for specific monogenic disorders (N = 7). Fetal trophoblasts were enriched and stained using magnetic activated cell sorting and isolated by fluorescens activated single-cell sorting. Individual cells were subject to whole genome amplification, and cells of fetal origin were identified by DNA-profiling using short tandem repeat markers. The amplified fetal DNA was input for genetic testing for autosomal dominant-, autosomal recessive-, X-linked and repeat expansion disorders by direct variant analysis and haplotyping. The cell-based NIPT results were compared with those of invasive testing.Results: In two cases at risk of skeletal dysplasia, caused by variants in the FGFR3 gene (autosomal dominant disorders), cell-based NIPT correctly stated an affected fetus, but allelic dropout of the normal alleles were observed in both cases. Cell-based NIPT gave an accurate result in two cases at risk of autosomal recessive disorders, where the parents carried either different diastrophic dysplasia causing variants in the SLC26A2 gene or the same cystic fibrosis disease-causing variant in the CFTR gene. Cell-based NIPT accurately identified an affected male fetus in a pregnancy at risk of Duchenne muscular dystrophy (DMD gene, X-linked recessive disorders). In two cases at risk of the myotonic dystrophy type 1 (DMPK gene, repeat expansion disorder), cell-based NIPT correctly detected an affected and an unaffected fetus, respectively.Discussion: Circulating fetal cells can be used to detect both maternally- and paternally inherited monogenic disorders irrespective of the type of variant, however, the risk of allelic dropout must be considered. We conclude that the clinical interpretation of the cell-based NIPT result thus varies depending on the disorders’ mode of inheritance.https://www.frontiersin.org/articles/10.3389/fgene.2023.1188472/fullnoninvasive prenatal testingfetal cellsextravillous trophoblastsmonogenic disordersrepeat expansion disordersclinical interpretation |
| spellingShingle | Line Dahl Jeppesen Line Dahl Jeppesen Lotte Hatt Ripudaman Singh Palle Schelde Katarina Ravn Christian Liebst Toft Christian Liebst Toft Maria Bach Laursen Jakob Hedegaard Inga Baasch Christensen Bolette Hestbek Nicolaisen Lotte Andreasen Lars Henning Pedersen Lars Henning Pedersen Lars Henning Pedersen Ida Vogel Ida Vogel Dorte Launholt Lildballe Dorte Launholt Lildballe Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls Frontiers in Genetics noninvasive prenatal testing fetal cells extravillous trophoblasts monogenic disorders repeat expansion disorders clinical interpretation |
| title | Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls |
| title_full | Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls |
| title_fullStr | Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls |
| title_full_unstemmed | Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls |
| title_short | Clinical interpretation of cell-based non-invasive prenatal testing for monogenic disorders including repeat expansion disorders: potentials and pitfalls |
| title_sort | clinical interpretation of cell based non invasive prenatal testing for monogenic disorders including repeat expansion disorders potentials and pitfalls |
| topic | noninvasive prenatal testing fetal cells extravillous trophoblasts monogenic disorders repeat expansion disorders clinical interpretation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1188472/full |
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