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

Abstract

haracterisation 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 Abstract 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.

Two distinctive classic genetic syndromes, 22q11.2 deletion syndrome and Angelman syndrome, occurring within the same family

“…Interestingly, the reciprocal balanced translocation occurred in the proximity of the VCFS and PWS/AS critical regions, both of which are susceptible to microdeletions mediated by intrachromosomal recombination between low copy repeats within the genome [Amos‐Landgraf et al, 1999; Edelmann et al, 1999a]. Recently, the involvement of microdeletion syndrome‐associated regions in balanced translocations has been documented in several syndromes, including those involving the VCFS critical region [Spiteri et al, 2003], the PWS/AS critical region [Mignon‐Ravix et al, 2007], and the Williams syndrome critical region on 7q11.23 [Portera et al, 2006]. It is tempting to speculate that these genome architectural features of 22q and 15q might have led to the formation of the chromosomal translocation between the two chromosomes in an ancestor of the mother.…”