Identification of a novel mutation of SH3BP2 in cherubism and demonstration that SH3BP2 mutations lead to increased NFAT activation

Hum Mutat. 2006 Jul;27(7):717-8. doi: 10.1002/humu.9433.


We describe a novel missense mutation (Aspartic acid to Asparagine, p.D419N (g.1371G>A, c.1255G>A) within exon 9 of SH3BP2 in a patient with cherubism, an autosomal dominant syndrome characterized by excessive osteoclastic bone resorption of the jaw. Two siblings and the father were carriers but lacked phenotypic features. Transient expression of p.D419N (c.1255G>A), as well as three previously described exon 9 mutations from cherubism patients (p.R415Q (c.1244G>A), p.D420E (c.1259G>A), and p.P418R (c.1253C>G)) increased activity of NFAT (nuclear factor of activated T-cells), an osteoclastogenic mediator, indicating that cherubism results from gain of function mutations in SH3BP2.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alleles
  • Cherubism / diagnostic imaging
  • Cherubism / genetics*
  • Cherubism / metabolism
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Heterozygote
  • Humans
  • Jurkat Cells
  • Male
  • Mutagenesis, Site-Directed
  • Mutation, Missense*
  • NFATC Transcription Factors / metabolism*
  • Pedigree
  • Radiography


  • Adaptor Proteins, Signal Transducing
  • NFATC Transcription Factors
  • SH3BP2 protein, human