Detection of a concomitant distal deletion in an inverted duplication of chromosome 3. Is there an overall mechanism for the origin of such duplications/deficiencies?

Abstract

We describe the first inverted duplication of the p21.3p26 region of chromosome 3 in a child with phenotypic features of the trisomy 3p syndrome. This uncommon type of aberration was verified by multicolour fluorescence in situ hybridisation (FISH) using yeast artificial chromosome (YAC) clones from chromosome 3 (CEPH library). With a newly constructed YAC clone from the 3p26 region an unexpected subtelomeric deletion was diagnosed in the aberrant chromosome 3. Using the primed in situ labelling (PRINS) method, telomeres were found to be present on the recombinant chromosome 3. The repeated appearance of concomitant distal deletions in inverted duplications suggests that an overall mechanism exists for the origin of such duplications/ deficiencies.

Loss of subtelomeric sequence associated with a terminal inversion duplication of the short arm of chromosome 4

“…Subsequently, all additional cases of 8p terminal inversion duplications studied by FISH or molecular analyses were also shown to have similar loss of subtelomeric sequences [De DieSmulders et al, 1995;Guo et al, 1995;Floridia et al, 1996]. FISH analysis of terminal inversion duplications of 1q, 2q, 3p, 5p, 7q, and the proposita also showed loss of subtelomeric regions [Mewar et al, 1994;Stetten et al, 1997;Jenderny et al, 1998;Sreekantaiah et al, 1999;Bonaglia et al, 2000;Kennedy et al, 2000].…”

“…These were proposed to arise from illegitimate recombination between inverted repeats in 8p during maternal meiosis, and are always associated with an 8p subtelomeric deletion [Floridia et al, 1996]. Terminal inversion duplications of other chromosomes were evaluated by¯uorescence in situ hybridization (FISH) analysis and small subtelomeric deletions have been identi®ed in most, but not all, cases [Mewar et al, 1994;Jenderny et al, 1998;Sreekantaiah et al, 1999;Kennedy et al, 2000;Tsezou et al, 2000]. Molecular analysis of several cases implied a post-zygotic or paternal meiosis-II origin for terminal inversion duplications of chromosomes other than 8p [Stetten et al, 1997;Kotzot et al, 2000;Tsezou et al, 2000].…”

A paternally derived inverted duplication of distal 14q with a terminal 14q deletion

“…The inverted duplication associated with a terminal deletion has been observed at various chromosomal ends such as 1q [Mewar et al, 1994;de Brasi et al, 2001], 2q [Bonaglia et al, 2000], 3p [Jenderny et al, 1998;Kennedy et al, 2000], 4p [Cotter et al, 2001;Kondoh et al, 2003], 4q [van Buggenhout et al, 2004], 5p [Sreekantaiah et al, 1999], 7q [Hoo et al, 1995;Stetten et al, 1997], 8p [Dill et al, 1987;Mitchell et al, 1994;Florida et al, 1996;Giglio et al, 2001], 9p [Teebi et al, 1993], 10p and 10q [Hoo et al, 1995], 11p [Fisher et al, 2002], 21q [Pangalos et al, 1992], and Xp [Milunsky et al, 1999]. Since the parental karyotypes were normal, the inv dup(14q) associated with a terminal 14q deletion in this report might have been caused by the simplest model involving a U-type exchange that caused an end-to-end fusion and that led to a dicentric chromosome; during anaphase, the dicentric chromosome could break and result in a chromosome with an inverted duplication and loss of chromosomal material distal to the site of recombination [Weleber et al, 1976;Mitchell et al, 1994; Weinstein et al [1977]; Sklower et al [1984]; Carr et al [1987]; Wakita et al [1988]; Masada et al [1989]; Schinzel [2001]; Sonoda et al [2001].…”

Molecular characterization of a new patient with a non‐recurrent inv dup del 2q and review of the mechanisms for this rearrangement

“…Initially, two meiotic models in which a dicentric chromosome is formed by U-type exchange [Weleber et al, 1976] or by non-allelic homologous recombination (NAHR) mediated by low-copy repeats (LCRs) [Floridia et al, 1996] were described. The main difference between these two meiotic models is the absence or presence of a single copy region between the duplicated and deleted segments, which should indicate that the breakage is symmetric or asymmetric, respectively [Jenderny et al, 1998]. A third model is based on a pre-meiotic telomere loss followed by a breakage-fusion-bridge (BFB) cycle, where the sister chromatid fusion by a non-homologous end joining (NHEJ) produces gametes with terminal deletions associated with interrupted inverted duplications [Ballif et al, 2003].…”