The gene for Cherubism maps to chromosome 4p16.3. J. Mangion¹, N. Rahman¹, S. Edkins¹, R. Barfoot¹, T. Nguyen¹, A. Sigurdsson¹, J.V. Townend², D.R. Fitzpatrick³, A.M. Flannagan⁴, M.R. Stratton¹. 1) Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK; 2) Department of Maxillofacial Surgery, St Richard's Trust, Chichester, West Sussex PO 19 4SE, UK; 3) Human and Clinical Genetics Unit, Molecular Medicine Centre, Western General Hospitals Trust, Edinburgh EH4 2XU, Scotland, UK; 4) Department of Histopathology, Imperial College School of Medicine at St Mary's. Norfolk Place, London W2 1PG, UK.

   Cherubism is a rare autosomal dominant disease of childhood characterised by proliferative lesions within the mandible and maxilla leading to prominence of the lower face and appearances reminiscent of Renaissance cherubs. Resolution of these bony abnormalities is often observed after puberty. Using two families with clinically, radiologically and/or histologically proven Cherubism, we have performed a genome wide linkage search and localised the gene to chromosome 4p16.3 with a maximum multipoint LOD score of 5.64. Both families showed evidence of linkage to this locus. Critical meiotic recombinants place the gene in a 3cM interval between D4S127 and 4p-telomere. Within this region a strong candidate is the gene for fibroblast growth factor receptor 3 (FGFR3), mutations in which have been implicated in a diverse set of disorders of bone development. Having screened a total of 7 families of cherubism by conformation-sensitive gel electerophoresis (CSGE), we have found no evidence of mutations within FGFR3. We also found no evidence for loss of heterozygosity (LOH) within this region when we analysed 13 mandibular biopsies with the characteristic features of cherubism from 8 affected individuals, indicating that cherubism is unlikely to be due to the inactivation of a tumor supressor gene. We are currently in the process of collecting further families, so that we can perform allelic association studies on approximately 20 families.