SOS1 – Hereditary Gingival Fibromatosis

Hereditary gingival fibromatosis (HGF) is a rare, benign overgrowth of gingival tissue with autosomal dominant inheritance and variable expressivity. Early linkage analyses in a three-generation pedigree (n=17) confirmed severe HGF in seven members but excluded SOS1 and the GINGF loci, underscoring locus heterogeneity of this disorder (PMID:22849749). Subsequent family studies, including a pedigree of a mother and three descendants, reinforced autosomal dominant transmission with high penetrance and marked variability in severity (PMID:32413193).

A recent whole-exome sequencing study of 13 individuals affected with HGF from four unrelated Brazilian families identified a frameshift insertion in SOS1 (c.3265_3266insTAAC (p.Pro1089LeufsTer19)) segregating with disease in two pedigrees (≥6 affected relatives) under an autosomal dominant model (PMID:35665929). This finding implicates haploinsufficiency of SOS1, a key Ras guanine–nucleotide exchange factor, in gingival fibroblast overproliferation, although no tissue-specific functional assays have been reported. Given evidence from only two families and the presence of SOS1-negative pedigrees, the overall association remains limited, warranting further replication in diverse cohorts.

Key Take-home: SOS1 c.3265_3266insTAAC is a recurrent loss-of-function variant in autosomal dominant HGF, but genetic heterogeneity mandates cautious interpretation in diagnostic settings.

References

• Oral diseases • 2013 • Linkage analysis confirms heterogeneity of hereditary gingival fibromatosis. PMID:22849749
• Special care in dentistry • 2020 • Nonsyndromic hereditary gingival fibromatosis: Characterization of a family and review of genetic etiology. PMID:32413193
• Unknown journal • 2022 • Hereditary gingival fibromatosis: WES reveals SOS1 and REST variants. PMID:35665929

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