Molecular cytogenetic characterization of the first reported case of inv dup del 20p compatible with a U-type exchange model

Inverted duplications with terminal deletions have been reported for an increasing number of chromosome ends. The best characterized and most frequent rearrangement reported involves the short arm of chromosome 8. It derives from non-allelic homologous recombination (NAHR) between two inverted LCRs (low copy repeats) of the olfactory receptor (OR) gene cluster during maternal meiosis. We report here on the cytogenetic characterization of the first inversion duplication deletion involving the short arm of chromosome 20 (inv dup del 20p) in an 18-month-old boy presenting with clinical signs consistent with 20p trisomy syndrome. This abnormality was suspected on karyotyping, but high-resolution molecular cytogenetic investigations were required to define the breakpoints of the rearrangement and to obtain insight into the mechanism underlying its formation. The duplicated region was estimated to be 18.16 Mb in size, extending from 20p13 to 20p11.22, and the size of the terminal deletion was estimated at 2.02 Mb in the 20p13 region. No single copy region was detected between the deleted and duplicated segments. As neither LCR nor inversion was identified in the 20p13 region, the inv dup del (20p) chromosome abnormality probably did not arise by NAHR. The most likely mechanism involves a break in the 20p13 region, leading to chromosome instability and reparation by U-type exchange or end-to-end fusion.