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

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.

• Authors: Annelies Dheedene, Tom Sante, Matthias De Smet, Jean-François Vanbellinghen, Bernard Grisart, Sarah Vergult, Sandra Janssens, Björn Menten
• Journal: Prenatal diagnosis (Prenat Diagn) Vol. 36 Issue 8 Pg. 699-707 (Aug 2016) ISSN: 1097-0223 [Electronic] England
• PMID: 27176606 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Chemical References

• DNA

Topics

• Chromosome Disorders (diagnosis, genetics)
• Chromosomes, Human, Pair 13 (genetics)
• Chromosomes, Human, Pair 18 (genetics)
• DNA (analysis, blood)
• DNA Copy Number Variations
• Down Syndrome (diagnosis, 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, genetics)
• Trisomy 13 Syndrome
• Trisomy 18 Syndrome