Prenatal diagnosis: the clinical usefulness of array comparative genomic hybridization

Array comparative genomic hybridization (aCGH) has been replacing karyotype in neurodevelopment diseases or intellectual disability cases. Regarding prenatal diagnosis (PND) karyotyping is still the criterion standard technique; nevertheless, the application of aCGH in this field has been increasing dramatically and some groups recommended it as the first-tier prenatal genetic test in cases of fetal ultrasound abnormalities. Despite aCGH greater resolution, the detection of variants of unknown significance (VOUS) is not desirable, so it's need some reflexion before generalized application on PND.

The aim of this study was to analyze the prevalence and type of copy number variants (CNVs) detected in the 55 PND samples collected from pregnancies with indication to perform aCGH.

aCGH was performed using Agilent 4 × 180K microarrays and results were analyzed using CytoGenomics software.

Eight (14.5%) cases had pathogenic or likely pathogenic CNVs. VOUS were found in 21.8% of the cases, but this frequency could be minimized if only large CNVs above 1 million base pairs that are outside the clinically curated targeted regions were considered.