title: Clinical outcome of subchromosomal events detected by whole-genome noninvasive prenatal testing.
abstract: OBJECTIVE
  A novel algorithm to identify fetal microdeletion events in maternal plasma has been developed and used in clinical laboratory-based noninvasive prenatal testing. We used this approach to identify the subchromosomal events 5pdel, 22q11del, 15qdel, 1p36del, 4pdel, 11qdel, and 8qdel in routine testing. We describe the clinical outcomes of those samples identified with these subchromosomal events.
  
  
  METHODS
  Blood samples from high-risk pregnant women submitted for noninvasive prenatal testing were analyzed using low coverage whole genome massively parallel sequencing. Sequencing data were analyzed using a novel algorithm to detect trisomies and microdeletions.
  
  
  RESULTS
  In testing 175,393 samples, 55 subchromosomal deletions were reported. The overall positive predictive value for each subchromosomal aberration ranged from 60% to 100% for cases with diagnostic and clinical follow-up information. The total false positive rate was 0.0017% for confirmed false positives results; false negative rate and sensitivity were not conclusively determined.
  
  
  CONCLUSIONS
  Noninvasive testing can be expanded into the detection of subchromosomal copy number variations, while maintaining overall high test specificity. In the current setting, our results demonstrate high positive predictive values for testing of rare subchromosomal deletions.
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Helgeson
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wardrop
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: T
authors.initials: T
authors.lastname: Boomer
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Almasri
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: W B
authors.initials: WB
authors.lastname: Paxton
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Saldivar
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Dharajiya
authors.affiliation: Sequenom Laboratories, Morrisville, NC, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Monroe
authors.affiliation: Sequenom Laboratories, Grand Rapids, MI, USA.|Department of Obstetrics, Gynecology and Reproductive Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Farkas
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Grosu
authors.affiliation: Sequenom Laboratories, San Diego, CA, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: McCullough
mesh_terms: D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D006801:Humans; D062145:Maternal Serum Screening Tests; D011247:Pregnancy