REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

Am J Hum Genet. 2017 Jul 6;101(1):149-156. doi: 10.1016/j.ajhg.2017.06.006.


Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor (REST) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.

Keywords: RE1-silencing transcription factor; REST; gingival fibromatosis; mosaic mutation; nonsense-mediated decay; whole-exome sequencing.

MeSH terms

  • Adolescent
  • Base Sequence
  • Chromosome Segregation / genetics
  • Exons / genetics*
  • Family
  • Female
  • Fibromatosis, Gingival / genetics*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Pedigree
  • Repressor Proteins / genetics*


  • RE1-silencing transcription factor
  • Repressor Proteins