The gene for cherubism maps to chromosome 4p16.3

Cherubism is a rare familial disease of childhood characterized by prolifer ative lesions within the mandible and maxilla that lead to prominence of th e lower face and an appearance reminiscent of the cherubs portrayed in Rena issance art. Resolution of these bony abnormalities is often observed after puberty. Many cases are inherited in an autosomal dominant fashion, althou gh several cases without a family history have been reported. Using two fam ilies with clinically, radiologically, and/or histologically proved cherubi sm, we have performed a genomewide linkage search and have localized the ge ne to chromosome 4p16.3, with a maximum multipoint LOD score of 5.64. Both families showed evidence of linkage to this locus. Critical meiotic recombi nants place the gene in a 3-cM interval between D4S127 and 4p-telomere. Wit hin this region a strong candidate is the gene for fibroblast growth factor receptor 3 (FGFR3); mutations in this gene have been implicated in a diver se set of disorders of bone development.