SNP‐based non‐invasive prenatal testing detects sex chromosome aneuploidies with high accuracy. (20th June 2013)

• Record Type: Journal Article
• Authors: Samango‐Sprouse, Carole; Banjevic, Milena; Ryan, Allison; Sigurjonsson, Styrmir; Zimmermann, Bernhard; Hill, Matthew; Hall, Megan P.; Westemeyer, Margaret; Saucier, Jennifer; Demko, Zachary; Rabinowitz, Matthew; Chitty, Lyn S.; Bianchi, Diana W.
• Is Part Of: Prenatal diagnosis. Volume 33:Number 7(2013:Jul.)
• Page Start: 643
• Page End: 649
• Publication Date: 2013-06-20
• Subjects: Prenatal diagnosis -- Periodicals; Fetus -- Diseases -- Diagnosis -- Periodicals; Electronic journals; 618.32075
• DOI: 10.1002/pd.4159
• Languages: English
• ISSNs: 0197-3851

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <sec id="pd4159-sec-0001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="pd4159-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="pd4159-sec-0003" sec-type="section"> <title>Results</title> <p>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%.</p> </sec> <sec id="pd4159-sec-0004" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>