Direct duplication 12p11.21–p13.31 mediated by segmental duplications: a new recurrent rearrangement?

Abstract

We describe the characterization of an interstitial duplication of 12p, dup(12)(p11.21p13.31), by array-CGH and FISH in a patient with mental retardation and dysmorphic features. The sequence analysis of the breakpoints revealed the presence of homologous low copy repeats (LCRs) flanking the duplication region, thus suggesting that they have mediated the rearrangement. Pip-maker analysis showed that a third cluster of homologous LCRs lie distally to the two mediating the 12p duplication. We hypothesize that this duplication might be a new recurrent rearrangement and that, thanks to the different orientations of the homologous regions lying within each cluster, the three clusters are responsible for at least some of the several 12p aneuploidies reported in the literature such as direct and inverted duplications, deletions and supernumerary analphoid chromosomes. Moreover, we excluded that polymorphic inversions between these three clusters are present in the normal population.

Duplication 12p and Pallister–Killian syndrome: A case report and review of the literature toward defining a Pallister–Killian syndrome minimal critical region

“…In addition to the new case reported here, we identified 21 reports describing a total of 26 individuals with 12p duplications of varying sizes (15 cases were partial 12p duplication, one case had partial 12p triplication and 10 cases had duplication of the entire 12p) [Armendares et al, 1975; Biederman et al, 1977; Tenconi et al, 1977; Hansteen et al, 1978; Parslow et al, 1979; Dallapiccola et al, 1980; Stengel‐Rutkowski et al, 1981; Ray et al, 1985; Rivera et al, 1987; Tayel et al, 1989; Pfeiffer et al, 1992; Zelante et al, 1994; Allen et al, 1996; Rauch et al, 1996; Back et al, 1997; Rivera et al, 1999; Tekin et al, 2001; Zumkeller et al, 2004; De Gregori et al, 2005; Tsai et al, 2005; Eckel et al, 2006; Liang et al, 2006; Cetin et al, 2011]. Ages of the patients described in the previously published case reports ranged from birth to 34 years.…”

“…Among the cases of partial 12p duplication, it is worth mentioning the case reported by De Gregori et al [2005]. They reported a case of partial 12p duplication from 12p11.21–12p13.31 with the telomeric breakpoint mapping to within 9.4 Mb of 12p13.31.…”

“…It is unlikely that the duplication described in this case overlaps with that of our case reported herein. The patient described by De Gregori et al [2005] had very minimal overlapping phenotypic features to that of 12p duplication and PKS, with full cheeks, wide nasal bridge, and developmental delay among the features frequently seen in 12p duplication. The absence of characteristic facial features in the case reported by De Gregori supports the hypothesis that the chromosomal region duplicated in the proposita described in this report represents a putative critical region for the PKS phenotype.…”

High-resolution mapping identifies a commonly amplified 11q13.3 region containing multiple genes flanked by segmental duplications

“…AmpliWcation at 17p11.2»p12 has been linked to the presence of SDs (van Dartel and Hulsebos 2004), but a general role for SD mediated ampliWcation is yet to be proven. However, the involvement of SDs in chromosomal deletions involved in genomic disorders as well as chromosomal duplications mediated by segmental duplications has been established (De Gregori et al 2005). For instance, congenital heart defects are associated with deletions on distal 8p (del8p) (Devriendt et al 1999) and recurrent translocations have been identiWed between 4p16 and 8p23 (Giglio et al 2002).…”

Digital Agenesia in Martina Franca Donkey Foal: A Case Report

“…Previous data have reported this genomic region as highly unstable [11]. Polymorphisms due to the accretion of duplicated genomic segments are common in mammalian genomes, in particular at centromeric and telomeric regions where they are usually silenced and show no effect on the phenotype [12][13][14][15]. In mammalian species, unexplored polymorphisms were identified in swine, sheep, stallions, and donkeys [16][17][18], and the technique also provided evidence for the presence of highly conserved repetitive DNA.…”