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

Malgorzata I Srebniak,Karin Em Diderich,Ingrid Mbh Van De Laar,Gretel O Oudesluijs,Marjan Boter,Renske Oegema,Maarten Fcm Knapen,Lutgarde Cp Govaerts,Robert-Jan H Galjaard,Titia Cohen-Overbeek,Diane Van Opstal,Marieke Joosten

doi:10.1186/1755-8166-5-14

Malgorzata I Srebniak, Karin Em Diderich + Show 10 more

Open Access

https://doi.org/10.1186/1755-8166-5-14

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Abstract

BackgroundWe 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/resultsFrom 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.ConclusionsPrenatal 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.

Highlights

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
The standard cytogenetic prenatal diagnosis often still includes time-consuming karyotyping followed by targeted FISH or MLPA analysis when a submicroscopic abnormality is suspected
Implementing rapid microarray technology in routine prenatal diagnosis will allow the detection of unbalanced chromosomal abnormalities in a shorter period of time with much better resolution than conventional karyotyping [4]

Summary

Introduction

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. 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.

Results

Conclusion