Opposite deletions/duplications of the X chromosome: two novel reciprocal rearrangements

Paralogous sequences on the same chromosome allow refolding of the chromoso me into itself and homologous recombination. Recombinant chromosomes have m icroscopic or submicroscopic rearrangements according to the distance betwe en repeats. Examples are the submicroscopic inversions of factorVIII, of th e IDS gene and of the FLN1/emerin region, all resulting from misalignment o f inverted repeats, and double recombination. Most of these inversions are of paternal origin possibly because the X chromosome at male meiosis is fre e to refold into itself for most of its length. We report on two de novo re arrangements of the X chromosome found in four hypogonadic females. Two of them had an X chromosome deleted for most of Xp and duplicated for a portio n of Xq and two had the opposite rearrangement (class I and class II rearra ngements, respectively). The breakpoints were defined at the level of conti guous YACs. The same Xp11.23 breakpoint was found in the four cases. That o f the long arm coincided in three cases (Xq21.3) and was more proximal in c ase 4 (Xq21.1). Thus class I rearrangements (cases 1 and 2) are reciprocal to that of case 3, whilst that of case 4 shares only the Xp breakpoint. The abnormal X was paternal in the three cases investigated. Repeated inverted sequences located at the breakpoints of rearrangements are likely to favou r the refolding of the paternal X chromosome and the recombination of the r epeats. The repeat at the Xp11 may synapse with either that at Xq21.3 or th at at Xq21.1. These rearrangements seem to originate as the Xq28 submicrosc opic inversions but they are identifiable at the microscopic level and resu lt from a single recombination event.