Assessing the utility of confirmatory studies following identification of large-scale genomic imbalances by...

The identification of clinically relevant genomic dosage anomalies assists in accurate diagnosis, prognosis, and medical management of affected individuals. Technological advancements within the field, such as the advent of microarray, have markedly increased the resolution of detection; however, clinical laboratories have maintained conventional techniques for confirmation of genomic imbalances identified by microarray to ensure diagnostic accuracy. In recent years the utility of this confirmatory testing of large-scale aberrations has been questioned but has not been scientifically addressed.

We retrospectively reviewed 519 laboratory cases with genomic imbalances meeting reportable criteria by microarray and subsequently confirmed with a second technology, primarily fluorescence in situ hybridization.

All genomic imbalances meeting reportable criteria detected by microarray were confirmed with a second technology. Microarray analysis generated no false-positive results.

Confirmatory testing of large-scale genomic imbalances (deletion of ≥150 kb, duplication of ≥500 kb) solely for the purpose of microarray verification may be unwarranted. In some cases, however, adjunct testing is necessary to overcome limitations inherent to microarray. A recommended clinical strategy for adjunct testing following identified genomic imbalances using microarray is detailed.