title: Noninvasive detection of fetal trisomy 21 by sequencing of DNA in maternal blood: a study in a clinical setting.
abstract: OBJECTIVE
  We sought to evaluate a multiplexed massively parallel shotgun sequencing assay for noninvasive trisomy 21 detection using circulating cell-free fetal DNA.
  
  
  METHODS
  Sample multiplexing and cost-optimized reagents were evaluated as improvements to a noninvasive fetal trisomy 21 detection assay. A total of 480 plasma samples from high-risk pregnant women were employed.
  
  
  RESULTS
  In all, 480 prospectively collected samples were obtained from our third-party storage site; 13 of these were removed due to insufficient quantity or quality. Eighteen samples failed prespecified assay quality control parameters. In all, 449 samples remained: 39 trisomy 21 samples were correctly classified; 1 sample was misclassified as trisomy 21. The overall classification showed 100% sensitivity (95% confidence interval, 89-100%) and 99.7% specificity (95% confidence interval, 98.5-99.9%).
  
  
  CONCLUSIONS
  Extending the scope of previous reports, this study demonstrates that plasma DNA sequencing is a viable method for noninvasive detection of fetal trisomy 21 and warrants clinical validation in a larger multicenter study.
authors.affiliation: Sequenom Inc., 3595 John Hopkins Ct., San Diego, CA 92121, USA.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ehrich
authors.forename: Cosmin
authors.initials: C
authors.lastname: Deciu
authors.forename: Tricia
authors.initials: T
authors.lastname: Zwiefelhofer
authors.forename: John A
authors.initials: JA
authors.lastname: Tynan
authors.forename: Lesley
authors.initials: L
authors.lastname: Cagasan
authors.forename: Roger
authors.initials: R
authors.lastname: Tim
authors.forename: Vivian
authors.initials: V
authors.lastname: Lu
authors.forename: Ron
authors.initials: R
authors.lastname: McCullough
authors.forename: Erin
authors.initials: E
authors.lastname: McCarthy
authors.forename: Anders O H
authors.initials: AO
authors.lastname: Nygren
authors.forename: Jarrod
authors.initials: J
authors.lastname: Dean
authors.forename: Lin
authors.initials: L
authors.lastname: Tang
authors.forename: Don
authors.initials: D
authors.lastname: Hutchison
authors.forename: Tim
authors.initials: T
authors.lastname: Lu
authors.forename: Huiquan
authors.initials: H
authors.lastname: Wang
authors.forename: Vach
authors.initials: V
authors.lastname: Angkachatchai
authors.forename: Paul
authors.initials: P
authors.lastname: Oeth
authors.forename: Charles R
authors.initials: CR
authors.lastname: Cantor
authors.forename: Allan
authors.initials: A
authors.lastname: Bombard
authors.forename: Dirk
authors.initials: D
authors.lastname: van den Boom
mesh_terms: D000293:Adolescent; D000328:Adult; D004247:DNA / Q000097:blood; D004314:Down Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011247:Pregnancy; D011296:Prenatal Diagnosis; D017422:Sequence Analysis, DNA / Q000379:methods; D055815:Young Adult
chemical_list: D004247:DNA