Diagnostic accuracy of random massively parallel sequencing for non-invasive prenatal detection of common autosomal aneuploidies: a collaborative study in Europe.

Abstract

OBJECTIVE:

The objective of this study is to validate the diagnostic accuracy of a non-invasive prenatal test for detecting trisomies 13, 18, and 21 for a population in Germany and Switzerland.

METHODS:

Random massively parallel sequencing was applied using Illumina sequencing platform HiSeq2000. Fetal aneuploidies were identified using a median absolute deviation based z-score equation. A bioinformatics algorithm based on guanine-cytosine normalization was applied after the data were unblinded. Results of massively parallel sequencing and invasive procedures were compared.

RESULTS:

Overall, 40/42 samples were correctly classified as trisomy 21-positive, including a translocation trisomy 21 [46,XY,der(13;21),+21] and a structural aberration of chromosome 21 [46,XX,rec(21)dup(21q)inv(21)(p12q21.1)] but not including a low percentage mosaic trisomy 21 [47,XY,+21/46,XY], [sensitivity: 95.2%; one-sided lower confidence limit: 85.8%]; 430/430 samples were correctly classified as trisomy 21-negative (specificity: 100%; one-sided lower CL: 99.3%). Using a new bioinformatics algorithm with guanine-cytosine normalization, detection of trisomy 21 was facilitated, and five of five trisomy 13 cases and eight of eight trisomy 18 cases were correctly identified.

CONCLUSION:

Our newly established non-invasive prenatal test allows detection of fetal trisomies 13, 18, and 21 with high accuracy in a population in Germany and Switzerland.

• Authors: Markus Stumm, Michael Entezami, Karsten Haug, Cornelia Blank, Max Wüstemann, Bernt Schulze, Gisela Raabe-Meyer, Maja Hempel, Markus Schelling, Eva Ostermayer, Sabine Langer-Freitag, Tilo Burkhardt, Roland Zimmermann, Tina Schleicher, Bernd Weil, Ulrike Schöck, Patricia Smerdka, Sebastian Grömminger, Yadhu Kumar, Wera Hofmann
• Journal: Prenatal diagnosis (Prenat Diagn) Vol. 34 Issue 2 Pg. 185-91 (Feb 2014) ISSN: 1097-0223 [Electronic] England
• PMID: 24222400 (Publication Type: Journal Article)
• Copyright: © 2013 John Wiley & Sons, Ltd.

Topics

• Adult
• Algorithms
• Amniocentesis
• Aneuploidy
• Chorionic Villi Sampling
• Chromosome Aberrations
• Chromosome Disorders (diagnosis, genetics)
• Chromosomes, Human, Pair 13 (genetics)
• Chromosomes, Human, Pair 18 (genetics)
• Down Syndrome (diagnosis, genetics)
• Female
• Germany
• High-Throughput Nucleotide Sequencing
• Humans
• Karyotyping
• Male
• Middle Aged
• Mosaicism
• Pregnancy
• Prenatal Diagnosis
• Sensitivity and Specificity
• Sequence Analysis, DNA
• Switzerland
• Trisomy (diagnosis, genetics)
• Trisomy 13 Syndrome
• Trisomy 18 Syndrome
• Young Adult