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Next generation sequencing as a new detection strategy for maternal cell contamination in clinical prenatal samples.

OBJECTIVES
The maternal cell contamination in chorionic villus or amniotic fluid presents a serious preanalytical risk for prenatal misdiagnosis. The following study presents and validates a novel process for identifying MCC by detecting short tandem repeat markers on Ion Proton system. Initially, MCC testing was performed during the detection of chromosomal abnormalities so as to improve the detection efficiency and accuracy of this method.


MATERIAL AND METHODS
More than 70 STR loci were selected to establish the detection progress. Capillary electrophoresis was used to compare the next generation sequencing detection results, as well as to identify the optimal STR on Ion Proton system. Evaluation criteria for maternal cell contamination were set, and the automated data analysis was performed. The detection sensitivity was validated via 4 groups with mixed samples and different proportions.


RESULTS
Consequently, twenty-three clinical samples were tested to evaluate the detection accuracy. In addition, 14 reli-able STR loci, which were stably detected in more than 25 samples, were found. The detection sensitivity in maternal cell contamination was no less than 20%, while its accuracy reached 100% in clinical samples.


CONCLUSIONS
Finally, we established and validated a novel detection procedure for maternal cell contamination in clinical prenatal samples using next generation sequencing. This procedure allowed us to simultaneously perform prenatal test-ing and MCC testing. Unlike the traditional capillary electrophoresis, this method is rapid, highly sensitive, and suitable for wide range of clinical applications.