Fibromatosis, Gingival, 1
A number sign (#) is used with this entry because of evidence that gingival fibromatosis-1 (GINGF1) is caused by heterozygous mutation in the SOS1 gene (182530) on chromosome 2p22. One such family has been reported.
DescriptionGingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva (summary by Hart et al., 2002).
Genetic Heterogeneity of Hereditary Gingival Fibromatosis
Other loci for gingival fibromatosis have been mapped to chromosome 5q (GINGF2; 605544), chromosome 2p23.3-p22.3 (GINGF3; 609955), and chromosome 11p15 (GINGF4; 611010). GINGF5 (617626) is caused by mutation in the REST gene (600571) on chromosome 4q12. There is some evidence for a locus on chromosome 2p16-p13 (see MAPPING).
Clinical FeaturesEmerson (1965) reported a family in which 13 individuals in 4 generations had gingival fibromatosis. Becker et al. (1967) described gingival fibromatosis without other features in mother, son, and daughter.
Although Zackin and Weisberger (1961) stated that there was 'slight hypertrichosis in all members' of the Italian family they studied (see 135400), they did not clearly state whether persons without gingival fibromatosis as well as those with it were hirsute. Witkop (1971) described an extensively affected kindred in which none of 13 examined cases and none of many others reportedly with the disorder had hypertrichosis.
Gorlin (1977) suggested that the disorder described by Chatterjee and Mazumder (1967) as 'fibroosseous dysplasia of the jaws' in a man and his 2 sons may have been gingival fibromatosis in an unusually neglected form. The tumorous involvement reached amazing proportions as shown in the published photographs. The father had progressive swelling of the upper jaw from childhood; involvement of the lower jaw was later in onset.
InheritanceJorgenson and Cocker (1974) stated that there are both dominant and recessive forms of gingival fibromatosis, with generalized and focal types being variable expression of the same disorder.
Both genetic and pharmacologically induced forms of gingival fibromatosis are known. The most common genetic form, hereditary gingival fibromatosis, is usually transmitted as an autosomal dominant trait, although sporadic cases are common and autosomal recessive inheritance has been reported. In most recessively inherited cases, gingival fibromatosis occurs as a part of a syndrome, e.g., 228560 and 266270. Syndromal forms of gingival fibromatosis, with autosomal dominant inheritance patterns, are represented by 135500 and 135400.
MappingHart et al. (1998) performed a genomewide search for linkage to polymorphic markers in an extended family with an autosomal dominant form of isolated gingival fibromatosis. They found a maximum lod score of 5.05 at theta = 0.00 for the 2p21 region, termed GINGF, bounded by loci D2S1788 and D2S441.
By genotyping 4 Chinese families with gingival fibromatosis using polymorphic microsatellite markers, Xiao et al. (2000) defined the disease locus as an 8.7-cM region on 2p21. This region overlaps by 3.8 cM with the previously reported GINGF locus.
Possible Locus on 2p26-p13
Shashi et al. (1999) performed additional linkage studies on a family with gingival fibromatosis linked to 2p21 reported by Hart et al. (1998) and molecular cytogenetic studies on a boy with gingival fibromatosis and a duplication involving 2p21-p13 described by Fryns et al. (1989). These analyses refined the GINGF locus in the family to an 8-Mb region on 2p21 flanked by D2S1788 and D2S2298. In the boy, the region of duplication was shown to be proximal to this candidate region. Shashi et al. (1999) concluded that there are 2 loci on chromosome 2p, one at 2p21 and another at 2p16-p13, associated with gingival fibromatosis.
Molecular GeneticsHart et al. (2002) identified a heterozygous frameshift mutation in the SOS1 gene (182530.0001) as the cause of autosomal dominant hereditary gingival fibromatosis in a large Brazilian family showing linkage to 2p21.
Population GeneticsThe estimated incidence of hereditary gingival fibromatosis is 1 in 750,000 (Pehlivan et al., 2009).