Molecular cytogenetic characterization of the first reported case of inv dup del 20p compatible with a U‐type exchange model

Abstract

Inverted duplications with terminal deletions have been reported for an increasing number of chromosome ends. The best characterized and most frequent rearrangement reported involves the short arm of chromosome 8. It derives from non-allelic homologous recombination (NAHR) between two inverted LCRs (low copy repeats) of the olfactory receptor (OR) gene cluster during maternal meiosis. We report here on the cytogenetic characterization of the first inversion duplication deletion involving the short arm of chromosome 20 (inv dup del 20p) in an 18-month-old boy presenting with clinical signs consistent with 20p trisomy syndrome. This abnormality was suspected on karyotyping, but high-resolution molecular cytogenetic investigations were required to define the breakpoints of the rearrangement and to obtain insight into the mechanism underlying its formation. The duplicated region was estimated to be 18.16 Mb in size, extending from 20p13 to 20p11.22, and the size of the terminal deletion was estimated at 2.02 Mb in the 20p13 region. No single copy region was detected between the deleted and duplicated segments. As neither LCR nor inversion was identified in the 20p13 region, the inv dup del (20p) chromosome abnormality probably did not arise by NAHR. The most likely mechanism involves a break in the 20p13 region, leading to chromosome instability and reparation by U-type exchange or end-to-end fusion.

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

“…They did not detect a single copy region but were able to narrow down the region ''fusion site'' to $11 Kb. Wang et al [2008], using array-CGH and FISH did not identify a single copy region exceeding 100 Kb in an inv dup del 5p and neither could Leclercq et al [2009] detect a single copy segment exceeding 6 Kb using an oligo array-CGH (244 K) in an inv dup del 20p. Duplicated and deleted regions, interrupted by a very small single copy segment, have only been reported on two occasions [Ballif et al, 2003;Bonaglia et al, 2009].…”

1.15 Mb microdeletion in chromosome band 20p13 associated with moderate developmental delay—Additional case and data's review

“…Our patient is another with a subtelomeric loss of 20p13 [Baker et al, 2002; Adeyinka et al, 2005; Leclercq et al, 2009; Stevens et al, 2009; McGill et al, 2010]. Apart from patients described in more detailed by McGill et al The others harbor deletions as a result of complex [Leclercq et al, 2009; Stevens et al, 2009] or familial rearrangements [Baker et al, 2002, Adeyinka et al, 2005]. In addition, there are previously described patients with terminal deletions of the short arm of chromosome 20 which encompass the JAG1 gene, known to cause Alagille syndrome [Krantz et al, 1997] as well as or cytogenetically visible aberrations [Schinzel, 2001].…”

Phenotypic features of a microdeletion in chromosome band 20p13: A case report and review of the literature

“…Although 20p13 deletions may be associated with developmental delays in motor and speech, mental retardation and epilepsy at various levels of severity, and facial dysmorphism (Moutton et al, ), the typical characteristics of such cases remain enigmatic, leading to diagnostic delays. Interestingly, previous studies showed that patients who simultaneously harbored a duplication and subtelomeric deletion of 20p exhibited facial dysmorphism, psychomotor retardation, delayed development, and speech difficulties (Leclercq et al, ; Trachoo, Assanatham, Jinawath, & Nongnuch, ). However, the precise mechanisms underlying duplications and/or deletions of the 20p13 chromosome band remain unclear and require further study.…”