title: Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes.
abstract: OBJECTIVE
  The purpose of this study was to estimate the performance of a single-nucleotide polymorphism (SNP)-based noninvasive prenatal test for 5 microdeletion syndromes.
  
  
  METHODS
  Four hundred sixty-nine samples (358 plasma samples from pregnant women, 111 artificial plasma mixtures) were amplified with the use of a massively multiplexed polymerase chain reaction, sequenced, and analyzed with the use of the Next-generation Aneuploidy Test Using SNPs algorithm for the presence or absence of deletions of 22q11.2, 1p36, distal 5p, and the Prader-Willi/Angelman region.
  
  
  RESULTS
  Detection rates were 97.8% for a 22q11.2 deletion (45/46) and 100% for Prader-Willi (15/15), Angelman (21/21), 1p36 deletion (1/1), and cri-du-chat syndromes (24/24). False-positive rates were 0.76% for 22q11.2 deletion syndrome (3/397) and 0.24% for cri-du-chat syndrome (1/419). No false positives occurred for Prader-Willi (0/428), Angelman (0/442), or 1p36 deletion syndromes (0/422).
  
  
  CONCLUSIONS
  SNP-based noninvasive prenatal microdeletion screening is highly accurate. Because clinically relevant microdeletions and duplications occur in >1% of pregnancies, regardless of maternal age, noninvasive screening for the general pregnant population should be considered.
authors.affiliation: Departments of Obstetrics and Gynecology and Pathology, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Wapner
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Babiarz
authors.affiliation: Departments of Obstetrics and Gynecology and Pathology, College of Physicians and Surgeons, Columbia University, New York, NY.
authors.forename: Brynn
authors.initials: B
authors.lastname: Levy
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Stosic
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zimmermann
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Styrmir
authors.initials: S
authors.lastname: Sigurjonsson
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wayham
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ryan
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Milena
authors.initials: M
authors.lastname: Banjevic
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Phil
authors.initials: P
authors.lastname: Lacroute
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Megan P
authors.initials: MP
authors.lastname: Hall
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Demko
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Asim
authors.initials: A
authors.lastname: Siddiqui
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rabinowitz
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Gross
authors.affiliation: Natera Inc., San Carlos, CA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hill
authors.affiliation: Division of Human Genetics, Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT. Electronic address: benn@uchc.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Benn
mesh_terms: D000465:Algorithms; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D062145:Maternal Serum Screening Tests; D060885:Multiplex Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011247:Pregnancy; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D013577:Syndrome
keywords: microdeletion; noninvasive prenatal testing; single-nucleotide polymorphism