Parental origin and mechanisms of formation of cytogenetically recognisable de novo direct and inverted duplications

Abstract

Cytogenetic, FISH, and molecular results of 20 cases with de novo tandem duplications of 18 diVerent autosomal chromosome segments are reported. There were 12 cases with direct duplications, three cases with inverted duplications, and five in whom determination of direction was not possible. In seven cases a rearrangement between non-sister chromatids (N-SCR) was found, whereas in the remaining 13 cases sister chromatids (SCR) were involved. Paternal and maternal origin (7:7) was found almost equally in cases with SCR (3:4) and N-SCR (4:3). In the cases with proven inversion, there was maternal and paternal origin in one case each. Twenty three out of 43 cytogenetically determined breakpoints correlated with common or rare fragile sites. In five cases, including all those with proven inverse orientation, all breakpoints corresponded to common or rare fragile sites. In at least two cases, one with an interstitial duplication (dup(19)(q11q13)) and one with a terminal duplication (dup(8) (p10p23)), concomitant deletions (del(8) (p23p23.3) and del(19)(q13q13)) were found. (J Med Genet 2000;37:281-286)

Discrepancies in cytogenetic results between different tissues in two fetuses with Wolf- Hirschhorn syndrome

“…Unfortunately, no material was left for FISH studies to elucidate the origin of the additional segment. However, inverted duplications close to telomeres often accompany a concomitant terminal deletion (Minelli et al, 1993;Kotzot et al, 2000). A similar case with an 11q+ karyotype from CVS, but 11q-in amniocytes, was reported by Porter et al (1999).…”

A Girl with 15q Overgrowth Syndrome and dup(15)(q24q26.3) that Included Telomeric Sequences

“…However, in the previous cases, the investigators did not specifically look for such repeat sequences. Actually, interstitial telomeres were found in a 9p duplication [26] but not in 12 terminal duplications involving diverse chromosomes [27]. In contrast, interstitial telomeric and/or subtelomeric sequences have been detected in both triplications alluded to in previous studies [7,8], in a tandem 15q telomeric translocation [28], as well as in 9/21 (43%) translocations and rings concerning chromosomes other than chromosome number 15 [29].…”

“…Otherwise, chromosome 15p heteromorphisms would imply that a paternal chromosome was involved in the duplication. Although a meiotic origin cannot be ruled out, it seems unlikely in the light of the requirement of a postzygotic "normalizing" deletion of the duplicated segment; however, at least 2 duplications of meiotic origin have been found in mosaic patients with a normal cell line [27,32]. Finally, the occurrence of 5 similar dup(15)(q24q26) indicates that these duplications may indeed represent another recurrent 15q genomic disorder comparable to the t(12;15)(p13;q25) typical of congenital fibrosarcoma [30].…”

A Family with an Inverted Tandem Duplication 5q22.1q23.2

“…The mechanism of the origin of pure tandem duplications is not fully understood, but it is assumed that they may arise from misalignment of homologous sequences by 3-break rearrangements, including a U-type rearrangement, or by 2-break reciprocal translocations between homologues, or even an early mitotic rearrangement [Van Dyke, 1988;Kotzot et al, 2000]. Our case displays a rather small inverted tandem duplication of chromosome 5q.…”