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

摘要: Objective—To develop a single nucleotide polymorphism- and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy. Methods—Fifteen aneuploid samples, including thirteen 45,X, two 47,XXY, one 47,XYY, along with 185 euploid controls, were analyzed. Cell-free DNA was isolated from maternal plasma, amplified multiplex PCR assay targeted 19,488 polymorphic loci covering chromosomes 13, 18, 21, X, Y, sequenced. Sequencing results analyzed using Bayesian-based maximum likelihood statistical method to determine copy number of interrogated chromosomes, calculating sample-specific accuracies. Results—Of the samples passed stringent quality control metric (93%), algorithm correctly identified at all five 187 for 934/935 correct calls as 9.4 weeks gestation. We detected 45,X 91.7% sensitivity (CI: 61.5-99.8%) 100% specificity 97.9-100%), 47,XXY 47,XYY. The average calculated accuracy 99.78%. Conclusion—This non-invasively 47,XYY fetuses cfDNA plasma high accuracies, thus offers noninvasive potential function routine screen allowing detection rarely diagnosed yet commonly occurring aneuploidies.