The donor chromosome breakpoint for a jumping translocation is associated with large low-copy repeats in 21q21.3

Abstract

Jumping translocations (JTs) are very rare chromosome aberrations, usually identified in tumors. We report a constitutional JT between donor chromosome 21q21.3→qter and recipients 13qter and 18qter, resulting in an ∼15.5-Mb proximal deletion 21q in a girl with mild developmental delay and minor dysmorphic features. Using fluorescence in situ hybridization (FISH) studies, we identified an ∼550-kb complex inter- and intra-chromosomal low-copy repeat (LCR) adjacent to the 21q21.3 translocation breakpoint. On the recipient chromosomes 13qter and 18qter, the telomeric sequences TTAGGG were retained. Genotyping revealed that the deletion was of maternal origin. We propose that genome architecture involving LCRs may be a major mechanism responsible for the origin of jumping translocations.

The conundrum of a jumping translocation (JT) in CVS from twins and review of JTs

“…Many of these JTs were positive for interstitial telomere sequences. Stankiewicz et al [2003] studied a JT in a girl with mental retardation and showed that the 21q21.3 donor site was in a low copy repeats (LCR).…”

“…So the recipient sites were more widely distributed in hematological malignancies than in constitutional JTs. Internal telomere sequences were found in most constitutional JTs studied [Rivera et al, 1990;Park et al, 1992;Rossi et al, 1993;Devriendt et al, 1997;Vermeesch et al, 1997;Jewett et al, 1998;Petit et al, 1998;Reddy and Murphy, 2000;Lefort et al, 2001;Sala et al, 2002;Stankiewicz et al, 2003;Zahed et al, 2004], but not in all JTs in hematological malignancies. It has been suggested that the extended proliferation of cancer cells during the premalignant stage, such as myelodysplasia, results in chromosomal instability due to the loss of telomeric functions.…”

“…About 27% donor sites and 5% recipient sites were in the interstitial euchromatin region. One such, 21q21.3 donor site was a LCR [Stankiewicz et al, 2003]. A telomere like sequences was identified at the breakpoint 9p11.1 [Sala et al, 2002].…”

A constitutional telomeric translocation showing meiotic instability

“…Again, 22q11 does not seem to contain a telomere-related sequence [Azzalin et al, 1997] to facilitate recombination with a true telomere. Stankiewicz et al [2003] reported a girl with mild developmental delay and minor dysmorphic features caused by a constitutional jumping translocation whereby part of the long arm of chromosome 21 (21q21.3 ! ter) was translocated onto 13qter and 18qter with a subsequent 15.5 Mb proximal deletion of chromosome 21.…”

“…ter) was translocated onto 13qter and 18qter with a subsequent 15.5 Mb proximal deletion of chromosome 21. The translocation was mediated by an approximately 550-kb complex inter-and intrachromosomal LCR adjacent to the 21q21.3 translocation breakpoint while the telomeric sequence of recipient chromosomes were intact [Stankiewicz et al, 2003].…”