Non-invasive prenatal diagnosis for translocation carriers-YES please or NO go?

M.I. Srebniak*, F.S. Jehee, M. Joosten, M. Boter, W.G. de Valk, R. van der Helm, E.A. Sistermans, E. Voorhoeve, S. Bhola, M.J.V. Hoffer, N. den Hollander, M.V.E. Macville, D. Van Opstal

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Introduction The presence of an unbalanced familial translocation can be reliably assessed in the cytotrophoblast of chorionic villi. However, carriers of a balanced translocation often decline invasive testing. This study aimed to investigate whether an unbalanced translocation can also be diagnosed in cell free DNA by whole-genome non-invasive prenatal screening (NIPS). Material and methods Pregnant women carrying a fetus with an unbalanced familial translocation, for whom NIPS as well as microarray data were available, were included in this retrospective assessment. NIPS was performed in the course of the TRIDENT study. Results In 12 cases, both NIPS and microarray data were available. In 10 of 12 cases the unbalanced translocation was correctly identified by NIPS without prior knowledge on parental translocation. One was missed because the fetal fraction was too low. One was missed because of technical restrictions in calling 16p gains. Conclusions This study supports the hypothesis that routine NIPS may be used for prenatal diagnosis of unbalanced inheritance of familial translocations, especially with prior knowledge of the translocation allowing focused examination of the involved chromosomal regions. Our study showed that routine shallow sequencing designed for aneuploidy detection in cell free DNA may be sufficient for higher resolution NIPS, if specialized copy number software is used and if sufficient fetal fraction is present.
Original languageEnglish
Pages (from-to)2036-2043
Number of pages8
JournalActa Obstetricia et Gynecologica Scandinavica
Issue number11
Early online date1 Sept 2021
Publication statusPublished - Nov 2021


  • cell free DNA screening
  • copy number variant analysis
  • fetal fraction
  • non-invasive prenatal screening
  • unbalanced translocation

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