title: Benefits and burdens of using a SNP array in pregnancies at increased risk for the common aneuploidies.
abstract: We present the nature of pathogenic SNP array findings in pregnancies without ultrasound (US) abnormalities and show the additional diagnostic value of SNP array as compared with rapid aneuploidy detection and karyotyping. 1,330 prenatal samples were investigated with a 0.5-Mb SNP array after the exclusion of the most common aneuploidies. In 2.7% (36/1,330) of the cases, pathogenic chromosome aberrations were found; a microscopically detectable abnormality in 0.7% and a submicroscopic aberration in 2%. Our results show that in addition to the age- or screening-related aneuploidy risk, in pregnancies without US abnormalities, there is a risk of 1:148 (9/1,330) for a (sub)microscopic abnormality associated with an early-onset often severe disease, 1:222 (6/1,330) for a submicroscopic aberration causing an early-onset disease, 1:74 (18/1,330) for carrying a susceptibility locus for a neurodevelopmental disorder, and 1:443 (3/1,330) for a late-onset disorder (hereditary neuropathy with liability to pressure palsies in all three cases). These risk figures are important for adequate pretest counseling so that prospective parents can make informed individualized choices between targeted prenatal testing and broad testing with SNP array. Based on our results, we believe if invasive testing is performed, SNP array should be the preferred cytogenetic technique irrespective of the indication.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Diane
authors.initials: D
authors.lastname: Van Opstal
authors.forename: Femke
authors.initials: F
authors.lastname: de Vries
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Govaerts
authors.forename: Marjan
authors.initials: M
authors.lastname: Boter
authors.forename: Debora
authors.initials: D
authors.lastname: Lont
authors.forename: Stefanie
authors.initials: S
authors.lastname: van Veen
authors.forename: Marieke
authors.initials: M
authors.lastname: Joosten
authors.forename: Karin
authors.initials: K
authors.lastname: Diderich
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: Galjaard
authors.forename: Malgorzata I
authors.initials: MI
authors.lastname: Srebniak
mesh_terms: D017668:Age of Onset; D000782:Aneuploidy; D002869:Chromosome Aberrations / Q000196:embryology; D005260:Female; D006801:Humans; D007621:Karyotyping; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*
keywords: RAD; VUS; advanced maternal age; amniotic fluid; chorionic villi; first trimester screening; prenatal SNP array; susceptibility loci; unexpected diagnoses; variable penetrance CNVs