Multicolor-FISH Characterization of a Prenatal Mosaicism for a Chromosomal Rearrangement Undetected by Molecular Cytogenetics

Cytogenet Genome Res. 2021;161(3-4):143-152. doi: 10.1159/000514592. Epub 2021 Apr 7.

Abstract

Fetal mosaicism for chromosomal rearrangements remains a challenge to diagnose, even in the era of whole-genome sequencing. We present here a case of fetal mosaicism for a chromosomal rearrangement explored in amniocytes and fetal muscle, consisting of a major cell population (95%) with partial monosomy 4q and a minor population (5%) with additional material replacing the 4qter deleted segment. Molecular techniques (MLPA, array-CGH) failed to assess the origin of this material. Only multicolor-FISH identified the additional segment on chromosome 4 as derived from chromosome 17. Due to the poor prognosis, the couple chose to terminate the pregnancy. Because of low-level mosaicism, chromosomal microarray analysis (CMA), now considered as first-tier prenatal genetic analysis, did not allow the identification of the minor cell line. In case of large CNVs (>5 Mb) detected by CMA, karyotyping may be considered to elucidate the mechanism of the underlying rearrangement and eliminate mosaicism.

Keywords: Chromosome rearrangement; Mosaicism; Multicolor-FISH; Prenatal diagnosis; aCGH.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromosome Painting / methods*
  • Chromosomes, Human, Pair 17 / genetics
  • Chromosomes, Human, Pair 4 / genetics
  • Comparative Genomic Hybridization
  • Cytogenetics / methods*
  • Female
  • Fetus / metabolism*
  • Humans
  • Karyotyping
  • Maternal Age
  • Mosaicism*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Translocation, Genetic / genetics*