title: Non-targeted whole genome 250K SNP array analysis as replacement for karyotyping in fetuses with structural ultrasound anomalies: evaluation of a one-year experience.
abstract: OBJECTIVE
  We evaluated both clinical and laboratory aspects of our new strategy offering quantitative fluorescence (QF)-PCR followed by non-targeted whole genome 250K single-nucleotide polymorphism array analysis instead of routine karyotyping for prenatal diagnosis of fetuses with structural anomalies.
  
  
  METHODS
  Upon the detection of structural fetal anomalies, parents were offered a choice between QF-PCR and 250K single-nucleotide polymorphism array analysis (QF/array) or QF-PCR and routine karyotyping (QF/karyo).
  
  
  RESULTS
  Two hundred twenty fetal samples were included. In 153/220 cases (70%), QF/array analysis was requested. In 35/153 (23%), an abnormal QF-PCR result was found. The remaining samples were analyzed by array, which revealed clinically relevant aberrations, including two known microdeletions, in 5/118 cases. Inherited copy number variants were detected in 11/118 fetuses, copy number variants with uncertain clinical relevance in 3/118 and homozygous stretches in 2/118. In 67/220 (30%) fetuses, QF/karyo was requested: 23/67 (34%) were abnormal with QF-PCR, and in 3/67, an abnormal karyotype was found.
  
  
  CONCLUSIONS
  Even though QF/array does not reveal a high percentage of submicroscopic aberrations in fetuses with unselected structural anomalies, it is preferred over QF/karyo, as it provides a whole genome scan at high resolution, without additional tests needed and with a low chance on findings not related to the ultrasound anomalies.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. b.faas@antrg.umcn.nl.
authors.forename: Brigitte H W
authors.initials: BH
authors.lastname: Faas
authors.forename: Ilse
authors.initials: I
authors.lastname: Feenstra
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Eggink
authors.forename: Angelique J A
authors.initials: AJ
authors.lastname: Kooper
authors.forename: Rolph
authors.initials: R
authors.lastname: Pfundt
authors.forename: John M G
authors.initials: JM
authors.lastname: van Vugt
authors.forename: Nicole
authors.initials: N
authors.lastname: de Leeuw
mesh_terms: D000328:Adult; D025063:Chromosome Disorders / Q000235:genetics*; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007621:Karyotyping / Q000379:methods* / Q000706:statistics & numerical data; D025202:Molecular Diagnostic Techniques / Q000379:methods / Q000706:statistics & numerical data; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction / Q000379:methods* / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D016216:Ultrasonography, Prenatal / Q000379:methods*