Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies

Prenat Diagn. 2015 Aug;35(8):801-9. doi: 10.1002/pd.4613. Epub 2015 Jun 24.

Abstract

Objectives: The implementation of chromosomal microarray analysis (CMA) in prenatal testing for all patients has not achieved a consensus. Technical alternatives such as Prenatal BACs-on-Beads(TM) (PNBoBs(TM) ) have thus been applied. The aim of this study was to provide the frequencies of the submicroscopic defects detectable by PNBoBs(TM) under different prenatal indications.

Methods: A total of 9648 prenatal samples were prospectively analyzed by karyotyping plus PNBoBs(TM) and classified by prenatal indication. The frequencies of the genomic defects and their 95%CIs were calculated for each indication.

Results: The overall incidence of cryptic imbalances was 0.7%. The majority involved the DiGeorge syndrome critical region (DGS). The additional diagnostic yield of PNBoBs(TM) in the population with a low a priori risk was 1/298. The prevalences of DGS microdeletion and microduplication in the low-risk population were 1/992 and 1/850, respectively.

Conclusions: The constant a priori risk for common pathogenic cryptic imbalances detected by this technology is estimated to be ~0.3%. A prevalence higher than that previously estimated was found for the 22q11.2 microdeletion. Their frequencies were independent of maternal age. These data have implications for cell-free DNA screening tests design and justify prenatal screening for 22q11 deletion, as early recognition of DGS improves its prognosis.

Publication types

  • Evaluation Study

MeSH terms

  • Adult
  • Chromosome Deletion*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / epidemiology
  • Chromosome Disorders / genetics
  • Chromosome Duplication*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Karyotyping / methods*
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Prevalence
  • Retrospective Studies
  • Sensitivity and Specificity