Centromere-telomere (12;8p) fusion, telomeric 12q translocation, and i(12p) trisomy

The concurrence of a short arm isochromosome and a translocation of the ent ire long arm of the same chromosome to a telomere of another chromosome, im plying trisomy for 4p, 5p. 7p, 9p, 10p or 12p, has been described in 13 pat ients. We have nov; used fluorescence in situ hybrization (FISH) to better characterize one of these rearrangements in which 12q was translocated to 8 pter, whereas 12p was converted in an isochromosome. An alphoid centromere- 12 repeat gave a strong signal oil the i(12p) and a weak but distinct signa l at the breakpoint junction of the der(8), whereas the pantelomeric probe revealed three clear hybridization sites on the der(8): one at each end and another at the breakpoint junction. These findings suggest that the prime event was a post-fertilization centric fission of chromosome 12 leading to the 12q translocation via a real centromere-telomere fusion and the i(12p). Alternatively, the crucial event may have been a centromere telomere recom bination. An interstitial telomere has been documented by means of FISH at the breakpoint junction of the sole derivative usually present in 20 consti tutional translocations including eight with a jumping behavior. In additio n, six other telomeric translocations defined by banding methods, including another case of 12q translocation/i(12p), have also been jumping ones. The se telomeric translocations have been de novo events and their proneness to exhibit a jumping behavior appears to be independent of the involved chrom osomes, size of the translocated segments, and concomitant abnormalities.