Haploinsufficiency of XPO1 and USP34 by a de novo 230 kb deletion in 2p15, in a patient with mild intellectual disability and cranio-facial dysmorphisms

Brain malformations in a patient with deletion 2p16.1: A refinement of the phenotype to BCL11A

“…Conversely, three patients with deletions in the same region of 2p15-16.1, but not involving BCL11A, did not reveal abnormalities on their imaging studies (Fig. 2) [Chabchoub et al, 2008;Fannemel and Barøy, 2014;Prontera et al, 2011]. The only other described patient in the literature with a microdeletion similar to this case, i.e.…”

“…Following the initial report in 2007 by Rajcan-Separovic et al [Rajcan-Separovic et al, 2007], there have been 15 patients reported in the literature with overlapping deletions in this region [Chabchoub et al, 2008;Fannemel and Barøy, 2014;Florisson et al, 2013;Félix and Petrin, 2010;Hancarova et al, 2013;Hucthagowder et al, 2012;Liang et al, 2009;Peter et al, 2014;Piccione et al, 2012;Prontera et al, 2011;de Leeuw et al, 2008], in addition to reports from public databases such as DECIPHER and ISCA [Firth et al, 2009;Miller et al, 2010] and other large studies assessing developmental delay and copy number variants [Cooper et al, 2011;Kaminsky et al, 2011]. All of the reported patients had varying degrees of developmental delay, along with shared dysmorphic features and microcephaly, making this a recognizable microdeletion syndrome.…”

“…Some of the reports of patients with 2p15-16.1 deletion have suggested narrowing the critical region of the neurodevelopmental phenotype to 4 genes; BCL11A, PAPOLG, REL and PEX13 [Hancarova et al, 2013;Liang et al, 2009;Piccione et al, 2012;de Leeuw et al, 2008]. However, haploinsufficiency of additional genes such as XPO1, USP34, VRK2 and KIAA1841 might also contribute to the phenotype associated with 2p15-16.1 syndrome which is suggestive of genetic and clinical heterogeneity [Chabchoub et al, 2008;Fannemel and Barøy, 2014]. Here we report an individual with brain malformations, developmental delay and distinctive facial features who has a deleted region encompassing only BCL11A.…”

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

“…Nevertheless, several deletions involving individual genes or smaller numbers of genes were reported (2)(3)(4)(5)(8)(9)(10) XPO1 (also known as CRM1) is a nuclear export receptor that exports approximately 200 different cargo molecules (e.g., proteins, rRNA, small nuclear RNA [snRNA], miR, and specific mRNAs) from the nucleus to the cytoplasm. This includes molecules required for correct neuronal positioning during development (20) or synaptogenesis (21).…”

De novo 2p16.1 microdeletion with metastatic esophageal adenocarcinoma

“…Other imaging findings described in subsequent case reports include leucoplakia, corpus callosum hypoplasia14 and a simplified cortical gyral pattern 15. However, other cases reported no brain abnormalities on imaging 11 12 15 16. Seizures were described in one case beginning at the age of 12 weeks, and this patient also had numerous renal cysts with nephrocalcinosis 14…”