title: Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell-free DNA from maternal plasma.
abstract: OBJECTIVE
  Whole-genome sequencing of circulating cell free (ccf) DNA from maternal plasma has enabled noninvasive prenatal testing for common autosomal aneuploidies. The purpose of this study was to extend the detection to include common sex chromosome aneuploidies (SCAs): [47,XXX], [45,X], [47,XXY], and [47,XYY] syndromes.
  
  
  METHODS
  Massively parallel sequencing was performed on ccf DNA isolated from the plasma of 1564 pregnant women with known fetal karyotype. A classification algorithm for SCA detection was constructed and trained on this cohort. Another study of 411 maternal samples from women with blinded-to-laboratory fetal karyotypes was then performed to determine the accuracy of the classification algorithm.
  
  
  RESULTS
  In the training cohort, the new algorithm had a detection rate (DR) of 100% (95%CI: 82.3%, 100%), a false positive rate (FPR) of 0.1% (95%CI: 0%, 0.3%), and nonreportable rate of 6% (95%CI: 4.9%, 7.4%) for SCA determination. The blinded validation yielded similar results: DR of 96.2% (95%CI: 78.4%, 99.8%), FPR of 0.3% (95%CI: 0%, 1.8%), and nonreportable rate of 5% (95%CI: 3.2%, 7.7%) for SCA determination
  
  
  CONCLUSIONS
  Noninvasive prenatal identification of the most common sex chromosome aneuploidies is possible using ccf DNA and massively parallel sequencing with a high DR and a low FPR.
authors.affiliation: Sequenom Center for Molecular Medicine, San Diego, CA, USA.
authors.forename: Amin R
authors.initials: AR
authors.lastname: Mazloom
authors.forename: Željko
authors.initials: Ž
authors.lastname: Džakula
authors.forename: Paul
authors.initials: P
authors.lastname: Oeth
authors.forename: Huiquan
authors.initials: H
authors.lastname: Wang
authors.forename: Taylor
authors.initials: T
authors.lastname: Jensen
authors.forename: John
authors.initials: J
authors.lastname: Tynan
authors.forename: Ron
authors.initials: R
authors.lastname: McCullough
authors.forename: Juan-Sebastian
authors.initials: JS
authors.lastname: Saldivar
authors.forename: Mathias
authors.initials: M
authors.lastname: Ehrich
authors.forename: Dirk
authors.initials: D
authors.lastname: van den Boom
authors.forename: Allan T
authors.initials: AT
authors.lastname: Bombard
authors.forename: Margo
authors.initials: M
authors.lastname: Maeder
authors.forename: Graham
authors.initials: G
authors.lastname: McLennan
authors.forename: Wendy
authors.initials: W
authors.lastname: Meschino
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Palomaki
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Canick
authors.forename: Cosmin
authors.initials: C
authors.lastname: Deciu
mesh_terms: D000782:Aneuploidy; D041321:Chromosomes, Human, X / Q000235:genetics; D041322:Chromosomes, Human, Y / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D005260:Female; D005333:Fetus / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009035:Mothers; D011247:Pregnancy / Q000097:blood; D011296:Prenatal Diagnosis / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D012729:Sex Chromosome Aberrations
chemical_list: D004247:DNA