Implementation of non-invasive prenatal testing by semiconductor sequencing in a genetic laboratory

Prenat Diagn. 2016 Aug;36(8):699-707. doi: 10.1002/pd.4841. Epub 2016 Jul 1.

Abstract

Objectives: To implement non-invasive prenatal testing (NIPT) for fetal aneuploidies with semiconductor sequencing in an academic cytogenomic laboratory and to evaluate the first 15-month experience on clinical samples.

Methods: We validated a NIPT protocol for cell-free fetal DNA sequencing from maternal plasma for the detection of trisomy 13, 18 and 21 on a semiconductor sequencing instrument. Fetal DNA fraction calculation for all samples and several quality parameters were implemented in the workflow. One thousand eighty-one clinical NIPT samples were analysed, following the described protocol.

Results: Non-invasive prenatal testing was successfully implemented and validated on 201 normal and 74 aneuploid samples. From 1081 clinical samples, 17 samples showed an abnormal result: 14 trisomy 21 samples, one trisomy 18 and one trisomy 16 were detected. Also a maternal copy number variation on chromosome 13 was observed, which could potentially lead to a false positive trisomy 13 result. One sex discordant result was reported, possibly attributable to a vanishing twin. Moreover, our combined fetal fraction calculation enabled a more reliable risk estimate for trisomy 13, 18 and 21.

Conclusions: Non-invasive prenatal testing for trisomy 21, 18 and 13 has a very high specificity and sensitivity. Because of several biological phenomena, diagnostic invasive confirmation of abnormal results remains required. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

MeSH terms

  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • Chromosomes, Human, Pair 13 / genetics
  • Chromosomes, Human, Pair 18 / genetics
  • DNA / analysis
  • DNA / blood*
  • DNA Copy Number Variations
  • Down Syndrome / diagnosis
  • Down Syndrome / genetics
  • False Positive Reactions
  • Female
  • Genetic Testing / methods
  • Humans
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Reproducibility of Results
  • Semiconductors*
  • Sensitivity and Specificity
  • Sequence Analysis, DNA / methods*
  • Trisomy / diagnosis
  • Trisomy / genetics
  • Trisomy 13 Syndrome
  • Trisomy 18 Syndrome

Substances

  • DNA