Dataset Information

A rare 3q13.31 microdeletion including GAP43 and LSAMP genes.

ABSTRACT: BACKGROUND:Interstitial deletions affecting the proximal long arm of chromosome 3 have been rarely reported in the literature. The deleted segments vary in localization and size with different breakpoints making genotype-phenotype correlation very difficult. Until now, a girl with a 1.9-Mb interstitial deletion of 3q13.2q13.31 and 14 novel patients with deletions in 3q11q23 have been reported. RESULTS:Here we report on a 7-year-old girl with neuropsychiatric disorders and renal, vascular and skeletal anomalies. Array-CGH analysis revealed a small rare inherited 3q13.31 deletion containing only two genes, GAP43 and LSAMP. The mutation analysis of the two genes was negative on the other non-deleted chromosome. GAP43 is considered a crucial component for an effective regenerative response in the nervous system and its mRNA is localized exclusively to nerve tissue where the protein is linked to the synaptosomal membrane. LSAMP is a 64- to 68-kD neuronal surface glycoprotein found in cortical and subcortical regions of the limbic system that acts as an adhesion molecule and guides the development of specific patterns of neuronal connection. The deleted region is adjacent to a "desert gene" region extending 2.099 Mb. CONCLUSIONS:We discuss the effects of GAP43 and LSAMP haploinsufficiency, proposing that their deletion may be responsible for the main phenotype. Further cases with similar microdeletion are expected to be diagnosed and will help to better characterize the clinical spectrum of phenotypes associated with 3q13.31 microdeletion.

SUBMITTER: Gimelli S

PROVIDER: S-EPMC3906914 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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A rare 3q13.31 microdeletion including GAP43 and LSAMP genes.

Gimelli Stefania S Leoni Massimiliano M Di Rocco Maja M Caridi Gianluca G Porta Simona S Cuoco Cristina C Gimelli Giorgio G Tassano Elisa E

Molecular cytogenetics 20131126 1

<h4>Background</h4>Interstitial deletions affecting the proximal long arm of chromosome 3 have been rarely reported in the literature. The deleted segments vary in localization and size with different breakpoints making genotype-phenotype correlation very difficult. Until now, a girl with a 1.9-Mb interstitial deletion of 3q13.2q13.31 and 14 novel patients with deletions in 3q11q23 have been reported.<h4>Results</h4>Here we report on a 7-year-old girl with neuropsychiatric disorders and renal, v ...[more]

PMID: 24279697

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Project description:Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system. NB is mainly driven by copy number alterations, such as MYCN amplification, large deletions of chromosome arm 11q and gain of chromosome arm 17q, which are all markers of high‑risk disease. Genes targeted by recurrent, smaller, focal alterations include CDKN2A/B, TERT, PTPRD and ATRX. Our previous study on relapsed NB detected recurrent structural alterations centered at limbic system‑associated membrane protein (LSAMP; HUGO Gene Nomenclature Committee: 6705; chromosomal location 3q13.31), which is a gene frequently reported to be deleted or downregulated in other types of cancer. Notably, in cancer, LSAMP has been shown to have tumor‑suppressing functions. The present study performed an expanded investigation using whole genome sequencing of tumors from 35 patients, mainly with high‑risk NB. Focal duplications or deletions targeting LSAMP were detected in six cases (17%), whereas single nucleotide polymorphism‑microarray analysis of 16 NB cell lines detected segmental alterations at 3q13.31 in seven out of the 16 NB cell lines (44%). Furthermore, low expression of LSAMP in NB tumors was significantly associated with poor overall and event‑free survival. In vitro, knockdown of LSAMP in NB cell lines increased cell proliferation, whereas overexpression decreased proliferation and viability. These findings supported a tumor suppressor role for LSAMP in NB. However, the higher incidence of LSAMP aberrations in cell lines and in relapsed NB tumors suggested that these alterations were a late event predominantly in advanced NB with a poor prognosis, indicating a role of LSAMP in tumor progression rather than in tumor initiation. In conclusion, the present study demonstrated recurrent genomic aberrations of chromosomal region 3q13.31 that targeted the LSAMP gene, which encodes a membrane protein involved in cell adhesion, central nervous system development and neurite outgrowth. The frequent aberrations affecting LSAMP, together with functional evidence, suggested an anti‑proliferative role of LSAMP in NB.

Dataset Information

A rare 3q13.31 microdeletion including GAP43 and LSAMP genes.

Publications

A rare 3q13.31 microdeletion including GAP43 and LSAMP genes.

Similar Datasets

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