Reliable detection of subchromosomal deletions and duplications using cell-based noninvasive prenatal testing

Prenat Diagn. 2018 Dec;38(13):1069-1078. doi: 10.1002/pd.5377. Epub 2018 Nov 19.


Objective: To gather additional data on the ability to detect subchromosomal abnormalities of various sizes in single fetal cells isolated from maternal blood, using low-coverage shotgun next-generation sequencing for cell-based noninvasive prenatal testing (NIPT).

Method: Fetal trophoblasts were recovered from approximately 30 mL of maternal blood using maternal white blood cell depletion, density-based cell separation, immunofluorescence staining, and high-resolution scanning. These trophoblastic cells were picked as single cells and underwent whole genome amplification for subsequent genome-wide copy number analysis and genotyping to confirm the fetal origin of the cells.

Results: Applying our fetal cell isolation method to a series of 125 maternal blood samples, we detected on average 4.17 putative fetal cells/sample. The series included 15 cases with clinically diagnosed fetal aneuploidies and five cases with subchromosomal abnormalities. This method was capable of detecting findings that were 1 to 2 Mb in size, and all were concordant with the microarray or karyotype data obtained on a fetal sample. A minority of fetal cells showed evidence of genome degradation likely related to apoptosis.

Conclusion: We demonstrate that this cell-based NIPT method has the capacity to reliably diagnose fetal chromosomal abnormalities down to 1 to 2 Mb in size.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Separation
  • Chromosome Aberrations*
  • Chromosome Deletion
  • DNA Copy Number Variations*
  • Female
  • Fluorescent Antibody Technique
  • Gene Deletion*
  • Gene Duplication*
  • Genotype
  • Humans
  • Karyotype
  • Male
  • Pregnancy
  • Prenatal Diagnosis
  • Single-Cell Analysis
  • Tissue Array Analysis
  • Trophoblasts / metabolism*
  • Young Adult