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

From May 2009 till June 2011 we performed HumanCytoSNP-12 array (HCS) (http://www.Illumina.com webcite) 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.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.Array based diagnosis of foetal unbalanced chromosome abnormalities has been successfully employed on prenatal material [1,2]. However, the standard cytogenetic prenatal diagnosis often still includes time-consuming karyotyping followed by targeted FISH or MLPA analysis when a submicroscopic abnormality is suspected. Although foetal anomalies are a strong indication of a genetic abnormality, chromosome analysis can only detect aberrations in about one fifth of cases [3]. In 1999-2010 we tested 3076 cases of foetuses with abnormal ultrasound findings and 21,7% (665) had an abnormal karyotype (including triploidy, trisomy 13, 18, 21 and aneuploidies of X and Y chromosome).Prenatal genetic diagnosis after ultrasound detection of foetal abnormalities requires a fas