Genomic SNP array as a gold standard for prenatal diagnosis of foetal ultrasound abnormalities.

Srebniak MI, Boter M, Oudesluijs GO, Cohen-Overbeek T, Govaerts LC, Diderich KE, Oegema R, Knapen MF, van de Laar IM, Joosten M, Van Opstal D, Galjaard RJ.

Abstract

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. Findings/results From May 2009 till June 2011 we performed HumanCytoSNP-12 array (HCS) (www.Illumina.com) analysis in 207 cases of foetal structural abnormalities. HCS allows detecting unbalanced genomic abnormalities with a resolution of about 150/200kb. 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.