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

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

Author information

1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
2
Baylor Genetics Laboratory, Houston, TX, USA.
3
RareCyte Inc., Seattle, WA, USA.
4
Immune Design, Seattle, WA, USA.
5
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
6
Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA.
7
Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA.

Abstract

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.

PMID:
30357877
DOI:
10.1002/pd.5377

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