Stabilization of a terminal inversion duplication of 8p by telomere capture from 18q

Abstract

Terminal inversion duplications of the short arm of chromosome 8 are one of the more common chromosome rearrangements in humans. We report an infant with multiple congenital anomalies, in whom karyotype analysis showed a terminal inversion duplication of 8p including additional material at the distal end of the derivative chromosome, shown to be of chromosome 18q origin. Terminal inversion duplications of 8p are the result of meiotic recombination between inverted olfactory gene receptor repeats in 8p. This recombination generates a dicentric intermediate that breaks during anaphase, and the broken chromosome end is stabilized by telomere healing or telomere capture. The origin of the telomeric region in the majority of constitutional chromosome deletions studied to date was shown to be from telomere healing; the de novo addition of telomeric repeats. In the proband a cytogenetically detectable piece of chromosome 18q was present on the distal end of the derivative 8, suggesting that this chromosome was stabilized by telomere capture of 18q. FISH analyses of additional cases may yield information as to whether telomere capture or telomere-healing events are the predominant mechanism of chromosome stabilization in terminal inversion duplications of 8p.

Inverted duplications: how many of them are mosaic?

“…The same situation was reported in an inv dup(8p) stabilized by telomere capture from 18q. 29 The importance of the findings we discussed here relies on the fact that such mosaic situations with two or more cell lines, all with a different abnormality of the same chromosome, might not be rare. Beyond the three cases with the inv dup(8p)/del(8p) mosaicism, 17 -19 we were able to find in the literature four 5pÀ/5p þ cases ( 10 ; one studied by us) and several cases with a mosaicism consisting of a cell line with a dicentric isochromosome and another one with a deleted chromosome.…”

Ring chromosome formation as a novel escape mechanism in patients with inverted duplication and terminal deletion

“…Telomere healing can be accomplished by addition of human telomeric tandem repeat sequence to broken chromosome ends 20 Examples of constitutional telomere capture are less common and is only reported a few times. 22,23 Among the several inverted duplication/deletion events reported, 7 -9,15 -19,23 in a single case the broken chromosome was proven to be repaired with telomere capture. 23 On the contrary, in our case the healing of the broken end may have been mediated by ring formation.…”

“…22,23 Among the several inverted duplication/deletion events reported, 7 -9,15 -19,23 in a single case the broken chromosome was proven to be repaired with telomere capture. 23 On the contrary, in our case the healing of the broken end may have been mediated by ring formation. In an acrocentric chromosome, an additional break involving the short arm probably does not lead to an additional loss of coding sequence and consequently to impaired cell proliferation.…”

Inverted duplications deletions: underdiagnosed rearrangements??

“…On 2002, Kostiner et al, (54) described an inv dup del(8p) case having a cytogenetically detectable piece of chromosome 18q on the distal end of its short arm, suggesting that the chromosome was stabilized by telomere capture. We found two similar cases that, on the basis of subtelomeric FISH on a p+ chromosome, were originally interpreted as unbalanced translocations.…”