Genomic microarrays in prenatal diagnosis

Abstract

The application of microarray-based techniques for the diagnosis of genomic rearrangements has been steadily growing in popularity since its introduction in 2004. Given the many advantages of these techniques over conventional cytogenetics, there is increasing pressure towards their application in prenatal diagnosis. However, there remain several important issues that must be addressed. For example, microarray-based techniques (comparative genomic hybridization-based arrays and single nucleotide polymorphism-based arrays) allow detection of even very small genomic imbalances that can determine pathological clinical conditions. In addition, there are other copy number variations which represent normal variation, with no detectable effects on phenotype. Given the still incomplete knowledge of the changes in our genome and the associated phenotypes, microarray-based diagnosis is likely to find variants of uncertain and unknown clinical significance. The interpretation of these variants is now a major challenge for the medical geneticist, who often find it difficult to establish precise correlations between genotype and phenotype. There is sufficient available evidence to justify the use of microarray-based diagnostics for a select number of specific conditions, but there is also an inevitable trend towards ever wider application. It is very important that this drift does not progress in an unchecked and uncontrolled manner under the thrust of commercial interests. Therefore, we recommend that scientific societies be vigilant and take an advisory role in the adopting of these technologies as new scientific knowledge becomes available.

Keywords: Copy number variations, Genomic microarray analysis, Prenatal diagnosis

Core tip: Given its advantages over conventional karyotyping, there is an increasing interest in determining whether microarray technology will be similarly advantageous for the detection of fetal genomic imbalances in a prenatal setting. Several issues remain to be addressed, such as for which pregnancies comparative genomic hybridization-based arrays should be carried out (i.e., whether for all pregnancies or only for those with ultrasound abnormalities). Another area of uncertainty is the choice of array platform. This article aims to contribute to the discussions on genomic microarrays in prenatal diagnosis by examining the literature and existing guidelines, and giving an opinion on possible future developments and on how best to handle them.