A rare case of Beckwith–Wiedemann syndrome caused by a de novo microduplication at 11p15.5 of paternal origin

The 15q11-q13 region is characterized by high instability, mainly caused by the presence of several homologous segmental duplications. Although most of the mechanisms dealing with cryptic deletions and amplifications, including inv dup(15)s, have been partly characterized, less is known about the rare translocations involving this region. We characterized at the molecular level five unbalanced translocations having most of 15q transposed to the distal region of another chromosome, whereas the der(15)(pter→q11q13) was missing. Imbalances were associated with Prader–Willi syndrome in four patients and Angelman syndrome in one. Array-CGH analysis demonstrated that the recipient chromosome was unbroken in three cases, carried a cryptic terminal deletion in one case, and a large terminal deletion, already diagnosed by classical cytogenetics, in another one. We were able to clone the breakpoint junctions in two cases, whereas cloning was impaired by the complex genomic architecture of the region in two other cases and by mosaicism in the last case. The results demonstrate the occurrence of different breakpoints in the region and highlight some unexpected findings, suggesting, in some cases, complex mechanism of formation at the basis of this type of rearrangement.