title: Genomic SNP array as a gold standard for prenatal diagnosis of foetal ultrasound abnormalities.
abstract: BACKGROUND
  We have investigated whether replacing conventional karyotyping by SNP array analysis in cases of foetal ultrasound abnormalities would increase the diagnostic yield and speed of prenatal diagnosis in clinical practice.
  
  
  RESULTS
  From May 2009 till June 2011 we performed HumanCytoSNP-12 array (HCS) (http://www.Illumina.com) analysis in 207 cases of foetal structural abnormalities. HCS allows detecting unbalanced genomic abnormalities with a resolution of about 150/200 kb. All cases were selected by a clinical geneticist after excluding the most common aneuploidies by RAD (rapid aneuploidy detection). Pre-test genetic counselling was offered in all cases.In 24/207 (11,6%) foetuses a clinically relevant genetic abnormality was detected. Only 8/24 abnormalities would have been detected if only routine karyotyping was performed. Submicroscopic abnormalities were found in 16/207 (7,7%) cases. The array results were achieved within 1-2 weeks after amniocentesis.
  
  
  CONCLUSIONS
  Prenatal SNP array testing is faster than karyotyping and allows detecting much smaller aberrations (~0.15 Mb) in addition to the microscopic unbalanced chromosome abnormalities detectable with karyotyping (~ > 5 Mb). Since karyotyping would have missed 66% (16/24) of genomic abnormalities in our cohort, we propose to perform genomic high resolution array testing assisted by pre-test counselling as a primary prenatal diagnostic test in cases of foetal ultrasound abnormalities.
authors.affiliation: Department of Clinical Genetics, Erasmus MC, Rotterdam, the Netherlands. m.srebniak@erasmusmc.nl.
authors.forename: Malgorzata I
authors.initials: MI
authors.lastname: Srebniak
authors.forename: Marjan
authors.initials: M
authors.lastname: Boter
authors.forename: Gretel O
authors.initials: GO
authors.lastname: Oudesluijs
authors.forename: Titia
authors.initials: T
authors.lastname: Cohen-Overbeek
authors.forename: Lutgarde Cp
authors.initials: LC
authors.lastname: Govaerts
authors.forename: Karin Em
authors.initials: KE
authors.lastname: Diderich
authors.forename: Renske
authors.initials: R
authors.lastname: Oegema
authors.forename: Maarten Fcm
authors.initials: MF
authors.lastname: Knapen
authors.forename: Ingrid Mbh
authors.initials: IM
authors.lastname: van de Laar
authors.forename: Marieke
authors.initials: M
authors.lastname: Joosten
authors.forename: Diane
authors.initials: D
authors.lastname: Van Opstal
authors.forename: Robert-Jan H
authors.initials: RJ
authors.lastname: Galjaard