Review of Chromosome aberration breakpoints in the context of ECARUCA (European Cytogeneticists Association Register of Unbalanced Chromosome Aberrations) Project
Within the ECARUCA project, molecular cytogenetic re-examinations were performed for European laboratories with the aim to better define breakpoints in various structural chromosome aberrations. As the main aim of the Register is to better know and understand the phenotype and course of rare chromosome aberrations, it was considered important to precisely define the aneuploid segments with respect to karyotype-phenotype correlation. For deletions and duplications, microsatellite marker analysis and FISH with BACs were the methods of choice. For additional marker chromosomes, chromosome dissection and reverse paiting was also applied. In selected cases also MLPA and array CGH was used. More than 100 patients were so far examined. The results of the studies proved to be very useful and not rarely surprising. The initial determination of breakpoints had to be revised in almost all cases. In some patients even the chromosome involved had not been correctly determined. Deletions in some cases concerned segments which were not even overlapping with the initially determined segment. Especially large was the discrepancy in instances of duplication-deletions. In addition, we re-investigated cases previously studied in our laboratory, partly referred from other countries in whom the determination of breakpoints and their publications date back to the pre-FISH period and needed to be worked up with the new molecular cytogenetic methods. With the cytogenetic workup of cases in the context of the ECARUCA project we were able to clarify and better determine many aberrations. In addition, however, we showed the necessity to reinvestigate previously determined structural chromosome aberrations with molecular methods since it is evident that in many patients in whom especially de novo duplications, interstitial deletions and additional marker chromosomes were determined and/or published the aberration(s) determined will be either incomplete or incorrect or both. This will result in many revisions of initial karyotypes and lead to much better karyotype-phenotype correlation and new insights into the impacts of chromosome aneuploidy in humans.