Evidence of genetic heterogeneity for hereditary gingival fibromatosis

Hereditary Gingival Fibromatosis (HGF) is the most common genetic form of g ingival fibromatosis. The condition is most frequently reported to be trans mitted as an autosomal-dominant trait, but autosomal-recessive inheritance has also been reported. The clinical presentation of HGF is variable, both in the distribution (number of teeth involved) and in the degree (severity) of expression. It is unknown if the variable clinical expression of HGF in different families is due to variable expression of a common gene mutation , allelic mutations, or nonallelic mutations. The apparently different mode s of Mendelian inheritance of HGF suggest genetic heterogeneity. A gene loc us for HGF has been localized to a 37-cM genetic interval on chromosome 2p2 1-p22 (D2S1352, Z(max), = 5.10, theta = 0.00) flanked by D2S1788 and D2S441 . To evaluate the generality of this linkage, we tested linkage with 9 mark ers from this candidate region in another large family, segregating for an autosomal-dominant form of generalized HGF, and found no support for linkag e with any of these markers. Furthermore, statistical tests of this apparen t heterogeneity were highly significant. Analysis of these data provides di rect evidence that at least two genetically distinct loci are responsible f or autosomal-dominant hereditary gingival fibromatosis.