The role of SH3BP2 in the pathophysiology of cherubism

Ernst J. Reichenberger, Michael A. Levine, Bjorn R. Olsen, Maria E. Papadaki, Steven A. Lietman

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress spontaneously thereafter. Most patients with cherubism have germline mutations in the gene encoding SH3BP2, an adapter protein involved in adaptive and innate immune response signaling. A mouse model carrying a Pro416Arg mutation in SH3BP2 develops osteopenia and expansile lytic lesions in bone and some soft tissue organs. In this review we discuss the genetics of cherubism, the biological functions of SH3BP2 and the analysis of the mouse model. The data suggest that the underlying cause for cherubism is a systemic autoinflammatory response to physiologic challenges despite the localized appearance of bone resorption and fibrous expansion to the jaws in humans.

Original languageEnglish (US)
Article numberS5
JournalOrphanet Journal of Rare Diseases
Issue numberSUPPL. 1
StatePublished - 2012
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)


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