Hereditary gingival fibromatosis: a case report with a novel SOS1 mutation and systematic review

Hereditary gingival fibromatosis (HGF) is a rare gingival disorder characterized by the slowly progressive, painless enlargement of the gums. This study aims to investigate a novel SOS1 mutation identified in a Chinese girl diagnosed with HGF. A comprehensive systematic review of the existing literature was conducted to enhance understanding of the clinical features and pathogenesis of HGF.

The proband was a 9-year-old girl from the Yi ethnic group who presented with gum overgrowth. Whole-exome sequencing (WES) and Sanger sequencing were used for mutation analysis. Histological features were analyzed using staining techniques. The pathogenicity of the identified variants was evaluated using SIFT2, PROVEAN, Polyphen-2_HDIV and MutationTaster. Alterations in protein structure were analyzed using AlphaFold3. A systematic literature review was conducted following PRISMA guidelines.

The patient presented with significant gingival overgrowth and hirsutism. Microscopic examination of the gingival specimens revealed elongated rete pegs penetrating into the fibrous connective tissue. Immunofluorescence staining indicated increased expression levels of MMP1, MMP3, and MMP13. WES identified 8 heterozygous variants, including a novel SOS1 mutation classified as potentially damaging. The systematic review included 52 articles, describing mutations in 23 genes and 12 chromosomal regions associated with HGF.

This study identifies a novel mutation in the known HGF-related gene SOS1, which may potentially contribute to gingival overgrowth by disrupting the interaction between SOS1 and Grb2.