Dataset Information

A novel mutation in the SH3BP2 gene causes cherubism: case report.

ABSTRACT: BACKGROUND: Cherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2) may be involved. CASE PRESENTATION: We investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, 17 were recruited for the genetic analysis. We conducted the direct sequence analysis of the SH3BP2 gene among these 17 family members. A disease-causing mutation was identified in exon 9 of the gene. It was an A1517G base change, which leads to a D419G amino acid substitution. CONCLUSION: To our knowledge, the A1517G mutation has not been reported previously in cherubism. This finding is novel.

SUBMITTER: Li CY

PROVIDER: S-EPMC1764878 | biostudies-literature | 2006

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A novel mutation in the SH3BP2 gene causes cherubism: case report.

Li Cui-Ying CY Yu Shi-Feng SF

BMC medical genetics 20061205

<h4>Background</h4>Cherubism is a rare hereditary multi-cystic disease of the jaws, characterized by its typical appearance in early childhood, and stabilization and remission after puberty. It is genetically transmitted in an autosomal dominant fashion and the gene coding for SH3-binding protein 2 (SH3BP2) may be involved.<h4>Case presentation</h4>We investigated a family consisting of 21 members with 3 female affected individuals with cherubism from Northern China. Of these 21 family members, ...[more]

PMID: 17147794

Similar Datasets

Project description:Cherubism (OMIM# 118400) is a genetic disorder with excessive jawbone resorption caused by mutations in SH3 domain binding protein 2 (SH3BP2), a signaling adaptor protein. Studies on the mouse model for cherubism carrying a P416R knock-in (KI) mutation have revealed that mutant SH3BP2 enhances tumor necrosis factor (TNF)-? production and receptor activator of nuclear factor-?B ligand (RANKL)-induced osteoclast differentiation in myeloid cells. TNF-? is expressed in human cherubism lesions, which contain a large number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells, and TNF-? plays a critical role in inflammatory bone destruction in homozygous cherubism mice (Sh3bp2(KI/KI) ). The data suggest a pathophysiological relationship between mutant SH3BP2 and TNF-?-mediated bone loss by osteoclasts. Therefore, we investigated whether P416R mutant SH3BP2 is involved in TNF-?-mediated osteoclast formation and bone loss. Here, we show that bone marrow-derived M-CSF-dependent macrophages (BMMs) from the heterozygous cherubism mutant (Sh3bp2(KI/+) ) mice are highly responsive to TNF-? and can differentiate into osteoclasts independently of RANKL in vitro by a mechanism that involves spleen tyrosine kinase (SYK) and phospholipase C?2 (PLC?2) phosphorylation, leading to increased nuclear translocation of NFATc1. The heterozygous cherubism mutation exacerbates bone loss with increased osteoclast formation in a mouse calvarial TNF-? injection model as well as in a human TNF-? transgenic mouse model (hTNFtg). SH3BP2 knockdown in RAW264.7 cells results in decreased TRAP-positive multinucleated cell formation. These findings suggest that the SH3BP2 cherubism mutation can cause jawbone destruction by promoting osteoclast formation in response to TNF-? expressed in cherubism lesions and that SH3BP2 is a key regulator for TNF-?-induced osteoclastogenesis. Inhibition of SH3BP2 expression in osteoclast progenitors could be a potential strategy for the treatment of bone loss in cherubism as well as in other inflammatory bone disorders.

Dataset Information

A novel mutation in the SH3BP2 gene causes cherubism: case report.

Publications

A novel mutation in the SH3BP2 gene causes cherubism: case report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets