A rare case of NIPT discrepancy caused by the placental mosaicism of three different karyotypes, 47,XXX, 47,XX,+21, and 48,XXX,+21

Mol Genet Genomic Med. 2020 Aug;8(8):e1279. doi: 10.1002/mgg3.1279. Epub 2020 May 28.

Abstract

Background: Placental mosaicism is one of the major reasons for noninvasive prenatal testing (NIPT) discrepancy. Herein, we discovered a rare case of placenta with complex karyotypes that caused false-positive and false-negative results in noninvasive prenatal testing.

Methods: Next-generation sequencing (NGS) and Quantitative fluorescent polymerase chain reaction (QF-PCR) were performed on the cord blood sample, fetal tissues, and eight placental biopsies. Fluorescent In Situ Hybridization (FISH) and karyotyping were also carried to confirm the fetal genome status.

Results: The results suggested that the fetal chromosome was 47,XXX and the placenta had three karyotypes of 48,XXX,+21, 47,XX,+21, and 47,XXX. QF-PCR indicated that the extra chromosome 21 and chromosome X were all from the father. It is speculated that the zygote may have 48,XXX,+21 karyotype and trisomy rescue could be the main mechanism for the development of the homogeneous fetus and complex mosaic placenta.

Conclusion: Overall, the complicated nature of our case underlines the importance of discussing with parents the possibility of both atypical and discordant results during preconfirmatory amniocentesis counseling and consent.

Keywords: NIPT; chromosomal abnormalities; confined placental mosaicism; prenatal diagnosis; trisomy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosomes, Human, X / genetics
  • Craniofacial Abnormalities / genetics*
  • Craniofacial Abnormalities / pathology
  • Down Syndrome / genetics*
  • Down Syndrome / pathology
  • False Negative Reactions
  • False Positive Reactions
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • In Situ Hybridization, Fluorescence / standards
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Karyotype*
  • Karyotyping / methods
  • Karyotyping / standards
  • Mosaicism*
  • Noninvasive Prenatal Testing / methods
  • Noninvasive Prenatal Testing / standards*
  • Placenta / metabolism
  • Placenta / pathology*
  • Pregnancy
  • Sex Chromosome Aberrations
  • Sex Chromosome Disorders of Sex Development / genetics*
  • Sex Chromosome Disorders of Sex Development / pathology
  • Trisomy / genetics*
  • Trisomy / pathology

Supplementary concepts

  • Tetrasomy X
  • Triple X syndrome