Secondary complex chromosome rearrangement identified by chromosome analysis and FISH subsequent to detection of an unbalanced derivative chromosome 12 by SNP array analysis.

Microarray analysis is used to detect small copy number changes (deletions and duplications) that may be associated with genetic syndromes and phenotypic abnormalities. However, there are limitations to what microarrays are able to detect. We present a patient referred for microarray in whom chromosome analysis identified a more complex structural rearrangement than was indicated by the microarray. Our studies included Affymetrix Cytoscan HD array, chromosome analysis and fluorescence in situ hybridization (FISH) using a subtelomere probe targeting chromosome 3. Array analysis revealed a 6.45-Mb terminal duplication of 3q28q29 and a 1.02-Mb terminal deletion of 12p13.33. This suggested an unbalanced translocation derivative. In order to investigate visibility of the rearrangement, chromosome analysis was performed, revealing an additional balanced complex chromosome rearrangement involving chromosomes 3 and 11, including a translocation with breakpoints at 3p13 and 11p11.2, as well as a paracentric inversion of segment 3p25p13 translocated onto chromosome 11. Subtelomere FISH confirmed that the duplicated chromosome 3q material observed in the array analysis was localized to distal 12p. This case clearly illustrates the combined utilization of classic cytogenetics, FISH and array technologies to better characterize chromosomal abnormalities.