title: Diagnostic accuracy of the BACs-on-Beads™ assay versus karyotyping for prenatal detection of chromosomal abnormalities: a retrospective consecutive case series.
abstract: OBJECTIVE
  To evaluate the diagnostic performance of the BACs-on-Beads(™) (BoBs(™)) assay for prenatal detection of chromosomal abnormalities.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Tertiary prenatal diagnosis centre.
  
  
  METHODS
  Women referred for prenatal diagnosis.
  
  
  METHODS
  We retrieved 2153 archived DNA samples collected between January 2010 and August 2011 for the BoBs(™) assay. These samples had previously been tested by quantitative fluorescence polymerase chain reaction (QF-PCR) and karyotyping. In the BoBs(™) assay a sample was defined as normal disomic when the ratio of the fluorescence intensities in a chromosome locus lay within the threshold (mean ratio ± 2SD), and as deleted or duplicated when the ratio was below the lower threshold (0.6-0.8) or above the upper threshold (1.3-1.4), respectively. The BoBs(™) results were further validated by microarray and compared in a blinded manner with the original QF-PCR and karyotyping results.
  
  
  METHODS
  Concordance of any numerical, structural, and submicroscopic chromosomal abnormalities between the methods.
  
  
  RESULTS
  BACs-on-Beads(™) was similar to karyotyping and QF-PCR in detecting trisomy 13, trisomy 18, trisomy 21, and sex chromosomal aneuploidies, and superior to QF-PCR in detecting major structural abnormalities (53.3 versus 13.3%) and mosaicism (28.6 versus 0%) involving chromosomal abnormalities other than the common aneuploidies. BoBs(™) detected six microdeletion syndromes missed by karyotyping and QF-PCR; however, BoBs(™) missed two cases of triploidy identified by QF-PCR. Therefore, the sensitivity of BoBs(™) is 96.7% (95% CI 92.6-98.7%), and its specificity is 100% (95% CI 99.8-100%).
  
  
  CONCLUSIONS
  BACs-on-Beads(™) can replace QF-PCR for triaging in prenatal diagnosis, and gives a better diagnostic yield than current rapid aneuploidy tests.
authors.affiliation: Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: K W
authors.initials: KW
authors.lastname: Choy
authors.forename: Y K
authors.initials: YK
authors.lastname: Kwok
authors.forename: Y K Y
authors.initials: YK
authors.lastname: Cheng
authors.forename: K M
authors.initials: KM
authors.lastname: Wong
authors.forename: H K
authors.initials: HK
authors.lastname: Wong
authors.forename: K O
authors.initials: KO
authors.lastname: Leung
authors.forename: K W
authors.initials: KW
authors.lastname: Suen
authors.forename: K
authors.initials: K
authors.lastname: Adler
authors.forename: C C
authors.initials: CC
authors.lastname: Wang
authors.forename: T K
authors.initials: TK
authors.lastname: Lau
authors.forename: M J
authors.initials: MJ
authors.lastname: Schermer
authors.forename: T T
authors.initials: TT
authors.lastname: Lao
authors.forename: T Y
authors.initials: TY
authors.lastname: Leung
mesh_terms: D000782:Aneuploidy; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis*; D002882:Chromosomes, Human, Pair 13; D002887:Chromosomes, Human, Pair 18; D004314:Down Syndrome / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007621:Karyotyping; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012729:Sex Chromosome Aberrations; D014314:Trisomy / Q000175:diagnosis*; D000073839:Trisomy 13 Syndrome; D000073842:Trisomy 18 Syndrome
keywords: BoBs™; QF-PCR; karyotyping; microdeletion