Exomic and transcriptomic alterations of hereditary gingival fibromatosis

Oral Dis. 2019 Jul;25(5):1374-1383. doi: 10.1111/odi.13093. Epub 2019 Apr 15.


Objective: Hereditary gingival fibromatosis (HGF) is a rare oral disease characterized by either localized or generalized gradual, benign, non-hemorrhagic enlargement of gingivae. Although several genetic causes of HGF are known, the genetic etiology of HGF as a non-syndromic and idiopathic entity remains uncertain.

Subjects and methods: We performed exome and RNA-seq of idiopathic HGF patients and controls, and then devised a computational framework that specifies exomic/transcriptomic alterations interconnected by a regulatory network to unravel genetic etiology of HGF. Moreover, given the lack of animal model or large-scale cohort data of HGF, we developed a strategy to cross-check their clinical relevance through in silico gene-phenotype mapping with biomedical literature mining and semantic analysis of disease phenotype similarities.

Results: Exomic variants and differentially expressed genes of HGF were connected by members of TGF-β/SMAD signaling pathway and craniofacial development processes, accounting for the molecular mechanism of fibroblast overgrowth mimicking HGF. Our cross-check supports that genes derived from the regulatory network analysis have pathogenic roles in fibromatosis-related diseases.

Conclusions: The computational approach of connecting exomic and transcriptomic alterations through regulatory networks is applicable in the clinical interpretation of genetic variants in HGF patients.

Keywords: TGF-beta signaling; hereditary gingival fibromatosis; multi-omics approach.

MeSH terms

  • Exome*
  • Fibroblasts
  • Fibromatosis, Gingival / genetics*
  • Gingiva
  • Humans
  • Transcriptome*