title: Implementation of non-invasive prenatal testing by semiconductor sequencing in a genetic laboratory.
abstract: OBJECTIVE
  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.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Dheedene
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Sante
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: De Smet
authors.affiliation: Plateforme de Biologie Moléculaire, Département des Laboratoires, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Vanbellinghen
authors.affiliation: Centre de Génétique Humaine, Institut de Pathologie et Génétique, Charleroi, Belgium.
authors.forename: Bernard
authors.initials: B
authors.lastname: Grisart
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Vergult
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Janssens
authors.affiliation: Center for Medical Genetics Ghent, Ghent University Hospital, Ghent University, Ghent, Belgium.
authors.forename: Björn
authors.initials: B
authors.lastname: Menten
mesh_terms: D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D004247:DNA / Q000032:analysis / Q000097:blood*; D056915:DNA Copy Number Variations; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D012666:Semiconductors; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D014314:Trisomy / Q000175:diagnosis / Q000235:genetics; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
chemical_list: D004247:DNA