Instability of Short Arm of Acrocentric Chromosomes: Lesson from Non-Acrocentric Satellited Chromosomes. Report of 24 Unrelated Cases.

Satellited non-acrocentric autosomal chromosomes (ps-qs-chromosomes) are the result of an interchange between sub- or telomeric regions of autosomes and the p arm of acrocentrics. The sequence homology at the rearrangement breakpoints appears to be, among others, the most frequent mechanism generating these variant chromosomes. The unbalanced carriers of this type of translocation may or may not display phenotypic abnormalities. With the aim to understand the causative mechanism, we revised all the ps-qs-chromosomes identified in five medical genetics laboratories, which used the same procedures for karyotype analysis, reporting 24 unrelated cases involving eight chromosomes. In conclusion, we observed three different scenarios: true translocation, benign variant and complex rearrangement. The detection of translocation partners is essential to evaluate possible euchromatic unbalances and to infer their effect on phenotype. Moreover, we emphasize the importance to perform both, molecular and conventional cytogenetics methods, to better understand the behavior of our genome.

Characterisation of a non-recurrent familial translocation t(7;9)(q11.23;p24.3) points to a recurrent involvement of the Williams-Beuren syndrome region in chromosomal rearrangements.

Recurrent and non-recurrent chromosomal rearrangements seem to reflect susceptibility to DNA rearrangements due to the presence of recombinogenic motifs in at least one partner chromosomal region. While specific genomic motifs such as AT-rich repeats, fragile sites and Alu repeats are often found in recurrent translocations, the molecular mechanisms underlying non-recurrent chromosomal rearrangements remain largely unknown. Here, we map the breakpoint region of a non-recurrent translocation, t(7;9)(q11.23;p24.3), present in a healthy woman who inherited the apparently balanced translocation from her mother and transmitted the same rearrangement to two sons-respectively healthy and aborted. Characterisation by a two-step FISH analysis, first with BAC clones and then with small locus-specific probes, restricted the breakpoint intervals to 8-10 kb. Both regions contained specific Alu sequences, which, together with the flanking low copy repeat block Ac in 7q11.23, might stimulate the translocation. We noted that, although the translocation is non-recurrent, 7q11.23 is recurrently involved in different chromosomal rearrangements, supporting the hypothesis that the 7q11.23 genomic structure is prone to recombination events.