title: Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies.
abstract: OBJECTIVE
  To demonstrate the usefulness of microarray testing in prenatal diagnosis based on our laboratory experience.
  
  
  METHODS
  Prenatal samples received from 2004 to 2011 for a variety of indications (n = 5003) were tested using comparative genomic hybridization-based microarrays targeted to known chromosomal syndromes with later versions of the microarrays providing backbone coverage of the entire genome.
  
  
  RESULTS
  The overall detection rate of clinically significant copy number alterations (CNAs) among unbiased, nondemise cases was 5.3%. Detection rates were 6.5% and 8.2% for cases referred with abnormal ultrasounds and fetal demise, respectively. The overall rate of findings with unclear clinical significance was 4.2% but would reduce to 0.39% if only de novo CNAs were considered. In cases with known chromosomal rearrangements in the fetus or parent, 41.1% showed CNAs related to the rearrangements, whereas 1.3% showed clinically significant CNAs unrelated to the karyotype. Finally, 71% of the clinically significant CNAs found by microarray were below the resolution of conventional karyotyping of fetal chromosomes.
  
  
  CONCLUSIONS
  Microarray analysis has advantages over conventional cytogenetics, including the ability to more precisely characterize CNAs associated with abnormal karyotypes. Moreover, a significant proportion of cases studied by array will show a clinically significant CNA even with apparently normal karyotypes.
authors.affiliation: Signature Genomic Laboratories, PerkinElmer, Inc., Spokane, WA, USA. lisa.shaffer@perkinelmer.com
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Shaffer
authors.forename: Mindy P
authors.initials: MP
authors.lastname: Dabell
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Fisher
authors.forename: Justine
authors.initials: J
authors.lastname: Coppinger
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bandholz
authors.forename: Jay W
authors.initials: JW
authors.lastname: Ellison
authors.forename: J Britt
authors.initials: JB
authors.lastname: Ravnan
authors.forename: Beth S
authors.initials: BS
authors.lastname: Torchia
authors.forename: Blake C
authors.initials: BC
authors.lastname: Ballif
authors.forename: Jill A
authors.initials: JA
authors.lastname: Rosenfeld
mesh_terms: D059786:Abnormal Karyotype / Q000196:embryology*; D002869:Chromosome Aberrations / Q000196:embryology; D055028:Comparative Genomic Hybridization; D005260:Female; D005313:Fetal Death / Q000235:genetics; D006801:Humans; D007621:Karyotyping / Q000379:methods; D046228:Microarray Analysis / Q000379:methods; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D011446:Prospective Studies; D017384:Sequence Deletion / Q000235:genetics; D016216:Ultrasonography, Prenatal