Investigation of the SH3BP2 gene mutation in cherubism

Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.