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SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy


  • Funding sources: This study was supported in part by a grant from the National Institute of Health, National Institute of Child Health and Human Development (4R44HD062114–02).

  • Conflicts of interest: M. B., A. R., S. S., B. Z., M. H., M. P. H., M. W., J. S., Z. D., and M. R. are employees of Natera.



This study aimed to develop a single-nucleotide polymorphism-based and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy.


Sixteen aneuploid samples, including thirteen 45,X, two 47,XXY, and one 47,XYY, along with 185 euploid controls, were analyzed. Cell-free DNA was isolated from maternal plasma, amplified in a single multiplex polymerase chain reaction assay that targeted 19 488 polymorphic loci covering chromosomes 13, 18, 21, X, and Y, and sequenced. Sequencing results were analyzed using a Bayesian-based maximum likelihood statistical method to determine copy number of interrogated chromosomes, calculating sample-specific accuracies.


Of the samples that passed a stringent quality control metric (93%), the algorithm correctly identified copy number at all five chromosomes in all but one of the 187 samples, for 934/935 correct calls as early as 9.4 weeks of gestation. We detected 45,X with 91.7% sensitivity (CI: 61.5–99.8%) and 100% specificity (CI: 97.9–100%), and 47,XXY and 47,XYY. The average calculated accuracy was 99.78%.


This method non-invasively detected 45,X, 47,XXY, and 47,XYY fetuses from cell-free DNA isolated from maternal plasma with high calculated accuracies and thus offers a non-invasive method with the potential to function as a routine screen allowing for early prenatal detection of rarely diagnosed yet commonly occurring sex aneuploidies. © 2013 John Wiley & Sons, Ltd.