Prenatal genetic diagnosis using microarray analysis in fetuses with congenital heart defects.

Objective: To evaluate the use of microarray analysis as a tool for the detection of submicroscopic chromosomal aberrations in prenatal diagnosis.

Methods: Twelve consecutive singleton fetuses with congenital heart defects but normal karyotype and normal fluorescence in situ hybridization results for the DiGeorge region were examined for chromosomal aberrations by genomic microarray analysis. Results were confirmed by fluorescence in situ hybridization and quantitative real time-polymerase chain reaction.

Results: At 1 Mb resolution, potentially causal copy number variations were identified in 3 out of 12 fetuses (25%) comprising a 9 Mb q terminal deletion on chromosome 15, a 3.5 Mb duplication in the critical region for the Potocki-Lupski syndrome on chromosome 17 and a mosaic trisomy 7. At higher resolution, aberrations with uncertain significance were identified in a further three cases (25%).

Conclusion: In our study, the application of microarray analysis in prenatal testing proved to be a valuable tool for the identification of submicroscopic chromosomal aberrations where conventional cytogenetic methods failed. Selection of appropriate resolution was found to be critical to obtain reliable, diagnostically conclusive data.