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

Prenat Diagn. 2014 Feb;34(2):185-91. doi: 10.1002/pd.4278. Epub 2013 Dec 12.


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.

MeSH terms

  • Adult
  • Algorithms
  • Amniocentesis
  • Aneuploidy
  • Chorionic Villi Sampling
  • Chromosome Aberrations
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • Down Syndrome / diagnosis*
  • Down Syndrome / 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*
  • Trisomy / genetics
  • Trisomy 13 Syndrome
  • Trisomy 18 Syndrome
  • Young Adult