De novo small supernumerary marker chromosomes detected on 143,000 consecutive prenatal diagnoses: chromosomal distribution, frequencies, and characterization combining molecular cytogenetics approaches

Prenat Diagn. 2014 May;34(5):460-8. doi: 10.1002/pd.4330. Epub 2014 Feb 11.

Abstract

Objective: The risk of clinical consequences in prenatal cases with de novo small supernumerary marker chromosomes (sSMC), often in mosaic conditions, is not easy to predict, which results in difficulties in genetic counseling.

Method: In this study, we evaluated the frequency, the chromosomal origin, and the clinical indication of 104 de novo sSMC detected in a monocenter survey on the basis of 143,000 consecutive prenatal diagnoses, and we assessed the reliability of molecular cytogenetics technologies for sSMC characterization.

Results: We detected a de novo sSMC frequency of 0.072%. Its incidence in advanced maternal age group is statistically different from that found in maternal anxiety indication (<35 years old). A higher prevalence of mosaicism in chorionic villi sampling (CVS) than in amniotic fluids was also revealed related to confined placental mosaicisms. The risk of confirmation in amniotic fluids of mosaics previously revealed at CVS was 33.3%. No uniparental disomy conditions were found when imprinted chromosomes were involved in the occurrence of de novo sSMC. The majority of de novo sSMC were acrocentric derived-chromosomes, and a neocentromere formation was observed in one pregnancy.

Conclusion: Our data support that array comparative genomic hybridization has improved sSMC characterization and demonstrate its utility in supporting genetic counseling. We propose a workflow for de novo sSMC characterization.

MeSH terms

  • Adult
  • Chromosome Aberrations / statistics & numerical data*
  • Chromosomes
  • Comparative Genomic Hybridization / methods
  • Comparative Genomic Hybridization / statistics & numerical data
  • Cytogenetic Analysis / methods*
  • Cytogenetic Analysis / statistics & numerical data
  • Female
  • Genetic Markers
  • Humans
  • Incidence
  • Male
  • Mosaicism / statistics & numerical data*
  • Pregnancy
  • Prenatal Diagnosis*
  • Reproducibility of Results

Substances

  • Genetic Markers