Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study

Diane Van Opstal*, Merel C. van Maarle, Klaske Lichtenbelt, Marjan M. Weiss, Heleen Schuring-Blom, Shama L. Bhola, Mariette J. V. Hoffer, Karin Huijsdens-van Amsterdam, Merryn V. Macville, Angelique J. A. Kooper, Brigitte H. W. Faas, Lutgarde Govaerts, Gita M. Tan-Sindhunata, Nicolette den Hollander, Ilse Feenstra, Robert-Jan H. Galjaard, Dick Oepkes, Stijn Ghesquiere, Rutger W. W. Brouwer, Lean BeulenSander Bollen, Martin G. Elferink, Roy Straver, Lidewij Henneman, Godelieve C. Page-Christiaens, Erik A. Sistermans, Dutch NIPT Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

53 Citations (Web of Science)

Abstract

Purpose: Noninvasive prenatal screening (NIPS) using cell-free DNA in maternal blood is highly sensitive for detecting fetal trisomies 21, 18, and 13. Using a genome-wide approach, other chromosome anomalies can also be detected. We report on the origin, frequency, and clinical significance of these other chromosome aberrations found in pregnancies at risk for trisomy 21, 18, or 13. Methods: Whole-genome shallow massively parallel sequencing was used and all autosomes were analyzed. Results: In 78 of 2,527 cases (3.1%) NIPS was indicative of trisomy 21, 18, or 13, and in 41 (1.6%) of other chromosome aberrations. The latter were of fetal (n = 10), placental (n = 22), maternal (n = 1) or unknown (n = 7). One case lacked cytogenetic follow-up. Nine of the 10 fetal cases were associated with an abnormal phenotype. Thirteen of the 22 (59%) placental aberrations were associated with fetal congenital anomalies and/or poor fetal growth (<p10), which was severe (<p2.3) in six cases. Conclusion: Genome-wide NIPS in pregnancies at risk for trisomy 21, 18, or 13, reveals a chromosomal aberration other than trisomy 21, 18 or 13 in about one-third of the abnormal cases. The majority involves a fetal or placental chromosome aberration with clinical relevance for pregnancy management.
Original languageEnglish
Pages (from-to)480-485
Number of pages6
JournalGenetics in Medicine
Volume20
Issue number5
DOIs
Publication statusPublished - 1 May 2018

Keywords

  • confined placental mosaicism
  • genome-wide NIPS
  • noninvasive testing
  • prenatal screening
  • trisomy 21
  • CONFINED PLACENTAL MOSAICISM
  • CELL-FREE DNA
  • PRENATAL-DIAGNOSIS
  • FOLLOW-UP
  • MATERNAL MALIGNANCIES
  • DUTCH LABORATORIES
  • TERM PLACENTAE
  • CVS MOSAICISM
  • FETAL DNA
  • ANEUPLOIDIES
  • CONFIRMATION
  • ANEUPLOIDY
  • ASSOCIATION
  • Chromosome Disorders/diagnosis
  • Trisomy
  • Humans
  • DNA Copy Number Variations
  • Female
  • Placenta/metabolism
  • Genomics/methods
  • Whole Genome Sequencing
  • Pregnancy
  • Prenatal Diagnosis/methods
  • Genetic Testing/methods
  • Chromosome Aberrations
  • Pregnancy Outcome

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