Intrachromosomal triplication of 2q11.2-q21 in a severely malformed infant: Case report and review of triplications and their possible mechanism

Abstract

A female fetus with brain malformations, multicystic kidneys, absence of the right thumb, and a posterior cleft of palate was delivered at 32 weeks of gestation. Cytogenetic studies including FISH showed a novel intrachromosomal triplication of the proximal long arm of chromosome 2 (q11.2-q21), resulting in tetrasomy for this segment. The middle repeat was inverted. At least 11 patients with intrachromosomal triplications have been reported, mostly involving chromosome 15q. The mechanism involved in formation of these rearrangements is compatible with U-type exchange events among three chromatids.

A new case of 2q duplication supports either a locus for orofacial clefting between markers D2S1897 and D2S2023 or a locus for cleft palate only on chromosome 2q13‐q21

“…Therefore, the orofacial clefting could be caused by a null mutation through disruption of a single dominant gene mapping at or near 2q13, as previously suggested by Riegel and Schinzel [2002]. Another patient with CPO and a triplication of 2q demonstrated different breakpoints [Wang et al, 1999], however, the triplication was only studied using G-banding and chromosome painting, and therefore, the location of the chromosomal breakpoints could be imprecise in that particular case. However, apart from the possibility of a disruption of a hypothetical single dominant gene for orofacial clefting (cleft lip/palate, CPO, and Pierre Robin sequence), a long distance effect of the duplication on such a dominant gene, or possible discussions on imprecise breakpoint determinations in chromosomal triplications not studied using FISH and locus specific DNA probes [Õ unap et al, 2005], another mechanism could apply.…”

“…Cytogenetic and FISH analysis showed a duplication of 2q13-q22. There have been only nine previous reports on a total of 10 patients with a pure duplication or triplication of the proximal chromosome 2q [Wang and Hunter, 1979;Mu et al, 1984;Lanman et al, 1986;Grevengood et al, 1993;Cooke et al, 1995;Glass et al, 1998;Wang et al, 1999;Riegel and Schinzel, 2002;Wegner et al, 2004]. Due to the variable clinical features and chromosomal breakpoints, no common pattern of a proximal duplication 2q syndrome could be defined from these cases, not even from the patients in whom breakpoints presumably were very similar [Riegel and Schinzel, 2002].…”

“…However, apart from the possibility of a disruption of a hypothetical single dominant gene for orofacial clefting (cleft lip/palate, CPO, and Pierre Robin sequence), a long distance effect of the duplication on such a dominant gene, or possible discussions on imprecise breakpoint determinations in chromosomal triplications not studied using FISH and locus specific DNA probes [Õ unap et al, 2005], another mechanism could apply. There have been four reports describing an association of CPO or Pierre Robin sequence, with either duplication or triplication of chromosome 2q13-q21 (Table II) [Lanman et al, 1986;Wang et al, 1999;Wegner et al, 2004;this report]. Another report has associated Pierre Robin sequence with larger duplications including the 2q13-q21 area [Glass et al, 1998].…”

“…Thus, we suggest the possibility that the overexpression of a gene(s) on chromosome 2q13-q21 may cause CPO and the Pierre Robin sequence. The case of CL/P [Riegel and Schinzel, 2002] (1) Wang and Hunter [1979]; (2) Mu et al [1984]; (3) Lanman et al [1986]; (4) Grevengood et al [1993]; (5) Cooke et al [1995]; (6-7) Glass et al [1998]; (8) Wang et al [1999]; (9) Riegel and Schinzel [2002]; (10) Wegner et al [2004].…”

“…Pure duplications/triplications of the proximal part of chromosome 2q have been rare. To our knowledge, only ten patients have been reported on [Wang and Hunter, 1979;Mu et al, 1984;Lanman et al, 1986;Grevengood et al, 1993;Cooke et al, 1995;Glass et al, 1998;Wang et al, 1999;Riegel and Schinzel, 2002;Wegner et al, 2004]. Clinical signs were variable and no specific 2q duplication syndrome could be defined so far [Bird and Mascarello, 2001;Riegel and Schinzel, 2002].…”