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Eur J Hum Genet. 2015 Oct;23(10):1286-93. doi: 10.1038/ejhg.2014.282. Epub 2015 Jan 14.

Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management.

Author information

1
Centre for Human Genetics, University Hospital Leuven, KU Leuven, Leuven, Belgium.
2
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
3
Department of Medical Genetics, University Medical Center Utrecht, AB Utrecht, The Netherlands.

Abstract

Noninvasive prenatal testing by massive parallel sequencing of maternal plasma DNA has rapidly been adopted as a mainstream method for detection of fetal trisomy 21, 18 and 13. Despite the relative high accuracy of current NIPT testing, a substantial number of false-positive and false-negative test results remain. Here, we present an analysis pipeline, which addresses some of the technical as well as the biologically derived causes of error. Most importantly, it differentiates high z-scores due to fetal trisomies from those due to local maternal CNVs causing false positives. This pipeline was retrospectively validated for trisomy 18 and 21 detection on 296 samples demonstrating a sensitivity and specificity of 100%, and applied prospectively to 1350 pregnant women in the clinical diagnostic setting with a result reported in 99.9% of cases. In addition, values indicative for trisomy were observed two times for chromosome 7 and once each for chromosomes 15 and 16, and once for a segmental trisomy 18. Two of the trisomies were confirmed to be mosaic, one of which contained a uniparental disomy cell line. As placental trisomies pose a risk for low-grade fetal mosaicism as well as uniparental disomy, genome-wide noninvasive aneuploidy detection is improving prenatal management.

PMID:
25585704
PMCID:
PMC4592078
DOI:
10.1038/ejhg.2014.282
[Indexed for MEDLINE]
Free PMC Article

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