What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping?
Abstract Background Balanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more eff...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Molecular Cytogenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13039-023-00657-x |
| _version_ | 1797556228057989120 |
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| author | Laura J. C. M. van Zutven Jona Mijalkovic Monique van Veghel-Plandsoen Margaret Goense Marike Polak Maarten F. C. M. Knapen Sabina de Weerd Marieke Joosten Karin E. M. Diderich Lies H. Hoefsloot Diane Van Opstal Malgorzata I. Srebniak |
| author_facet | Laura J. C. M. van Zutven Jona Mijalkovic Monique van Veghel-Plandsoen Margaret Goense Marike Polak Maarten F. C. M. Knapen Sabina de Weerd Marieke Joosten Karin E. M. Diderich Lies H. Hoefsloot Diane Van Opstal Malgorzata I. Srebniak |
| author_sort | Laura J. C. M. van Zutven |
| collection | DOAJ |
| description | Abstract Background Balanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more efficient way to identify couples at increased risk for carrying a balanced chromosome rearrangement. The aim of this study was to evaluate whether the potential fetal imbalances caused by parental balanced aberrations detected in our center are large enough to be detectable by genome-wide non-invasive prenatal testing (NIPT). Material and methods From January 1970 until May 2020 our laboratory received 30,863 unique requests for karyotyping due to RPL. We have identified 16,045 couples and evaluated all abnormal cytogenetic results to assess the minimal size of the involved chromosomal segments in potential unbalanced products of the rearrangements. Results In the presented cohort we detected 277 aberrant balanced translocations/inversions in females and 185 in males amongst 16,045 couples with RPL, which can be translated to a risk of 1:35 (2.9%, 95% CI 2.6–3.2%). Our study showed that the vast majority (98.7%, 95% CI 97.1–99.5%) of these balanced aberrations will potentially cause a fetal imbalance > 10 Mb, which is detectable with genome-wide NIPT if it was performed during one of the miscarriages. Conclusions Our study suggests that genome-wide NIPT is able to reveal most unbalanced products of balanced chromosomal rearrangements carried by couples with RPL and therefore can potentially identify balanced chromosomal aberration carriers. Moreover, our data suggest that these couples can be offered NIPT in case they decline invasive testing in future pregnancies. |
| first_indexed | 2024-03-10T16:59:50Z |
| format | Article |
| id | doaj.art-573fec928f5943d997613f1736ffc140 |
| institution | Directory Open Access Journal |
| issn | 1755-8166 |
| language | English |
| last_indexed | 2024-03-10T16:59:50Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
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| series | Molecular Cytogenetics |
| spelling | doaj.art-573fec928f5943d997613f1736ffc1402023-11-20T11:01:12ZengBMCMolecular Cytogenetics1755-81662023-09-011611810.1186/s13039-023-00657-xWhat proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping?Laura J. C. M. van Zutven0Jona Mijalkovic1Monique van Veghel-Plandsoen2Margaret Goense3Marike Polak4Maarten F. C. M. Knapen5Sabina de Weerd6Marieke Joosten7Karin E. M. Diderich8Lies H. Hoefsloot9Diane Van Opstal10Malgorzata I. Srebniak11Department of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Psychology, Education & Child Studies (DPECS), Erasmus UniversityDepartment of Obstetrics and Prenatal Medicine, Erasmus Medical CentreDepartment of Obstetrics and Gynaecology, Albert Schweitzer HospitalDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreDepartment of Clinical Genetics, Erasmus Medical CentreAbstract Background Balanced chromosome aberrations are reported in about 1:30 couples with recurrent pregnancy loss (RPL). Karyotyping of both parents is necessary to identify these aberrations. Genome-wide non-invasive prenatal testing (NIPT) in case of recurrent pregnancy loss could be a more efficient way to identify couples at increased risk for carrying a balanced chromosome rearrangement. The aim of this study was to evaluate whether the potential fetal imbalances caused by parental balanced aberrations detected in our center are large enough to be detectable by genome-wide non-invasive prenatal testing (NIPT). Material and methods From January 1970 until May 2020 our laboratory received 30,863 unique requests for karyotyping due to RPL. We have identified 16,045 couples and evaluated all abnormal cytogenetic results to assess the minimal size of the involved chromosomal segments in potential unbalanced products of the rearrangements. Results In the presented cohort we detected 277 aberrant balanced translocations/inversions in females and 185 in males amongst 16,045 couples with RPL, which can be translated to a risk of 1:35 (2.9%, 95% CI 2.6–3.2%). Our study showed that the vast majority (98.7%, 95% CI 97.1–99.5%) of these balanced aberrations will potentially cause a fetal imbalance > 10 Mb, which is detectable with genome-wide NIPT if it was performed during one of the miscarriages. Conclusions Our study suggests that genome-wide NIPT is able to reveal most unbalanced products of balanced chromosomal rearrangements carried by couples with RPL and therefore can potentially identify balanced chromosomal aberration carriers. Moreover, our data suggest that these couples can be offered NIPT in case they decline invasive testing in future pregnancies.https://doi.org/10.1186/s13039-023-00657-xRecurrent pregnancy lossNIPTKaryotypingBalanced translocationcfDNA |
| spellingShingle | Laura J. C. M. van Zutven Jona Mijalkovic Monique van Veghel-Plandsoen Margaret Goense Marike Polak Maarten F. C. M. Knapen Sabina de Weerd Marieke Joosten Karin E. M. Diderich Lies H. Hoefsloot Diane Van Opstal Malgorzata I. Srebniak What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping? Molecular Cytogenetics Recurrent pregnancy loss NIPT Karyotyping Balanced translocation cfDNA |
| title | What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping? |
| title_full | What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping? |
| title_fullStr | What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping? |
| title_full_unstemmed | What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping? |
| title_short | What proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell-free DNA genotyping? |
| title_sort | what proportion of couples with a history of recurrent pregnancy loss and with a balanced rearrangement in one parent can potentially be identified through cell free dna genotyping |
| topic | Recurrent pregnancy loss NIPT Karyotyping Balanced translocation cfDNA |
| url | https://doi.org/10.1186/s13039-023-00657-x |
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