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

• Published in: Prenatal diagnosis Vol. 34; no. 5; pp. 460 - 468
• Main Authors: Malvestiti, Francesca, De Toffol, Simona, Grimi, Beatrice, Chinetti, Sara, Marcato, Livia, Agrati, Cristina, Di Meco, Anna Maria, Frascoli, Giuditta, Trotta, Anna, Malvestiti, Barbara, Ruggeri, Anna, Dulcetti, Francesca, Maggi, Federico, Simoni, Giuseppe, Grati, Francesca Romana
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2014
• Subjects: 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
• ISSN: 0197-3851; 1097-0223
• DOI: 10.1002/pd.4330

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. © 2014 John Wiley & Sons, Ltd. What's already known about this topic? Frequency and characterization of de novo small supernumerary marker chromosomes detected in prenatal diagnosis on chorionic villi sampling and amniotic fluids. Predominance of markers derived from 15 samples and the association with maternal age. What does this study add? The rate of confirmation at amniocentesis of mosaic markers found in chorionic villi sampling considering the different combinations of the affected placental tissues and the lack of any uniparental disomy found for markers of imprinted chromosomes. Workflow for de novo marker characterization in prenatal diagnosis based on our experience of 143 000 consecutive cases.