Fluorescence in situ hybridization characterization of apparently balanced translocation reveals cryptic complex chromosomal rearrangements with unexpected level of complexity

The great majority of apparently balanced translocations are associated with multiple miscarriages and normal phenotype. Several mechanisms have been proposed to explain how a small percentage of apparently balanced translocations are associated with abnormal phenotypes. One of the proposed mechanisms that have not been well investigated is that apparently balanced translocations may host 'cryptic' complex chromosomal rearrangements (CCRs). To test this hypothesis, this study investigated 20 non-preselected cases with apparently balanced translocations in order to determine the presence of cryptic CCRs. Multiprobe subtelomeric and whole chromosome paint FISH analyses revealed and further characterized three cryptic CCRs. Two out of three CCRs showed an unexpected level of complexity. The results of this study provided evidence that the link between an apparently balanced rearrangement and the appearance of abnormal phenotype may be partly explained by the presence of cryptic CCRs. The results also suggested that what is reported as apparently balanced translocation by classical cytogenetics may host cryptic CCRs, which could be more common than initially thought. Furthermore, the use of both of the above-mentioned FISH methodologies was absolutely necessary to detect the CCRs. European Journal of Human Genetics ( 2004).