REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis

Baylor-Hopkins Center for Mendelian Genomics

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalAmerican Journal of Human Genetics
Volume101
Issue number1
DOIs
StatePublished - 6 Jul 2017
Externally publishedYes

Keywords

  • RE1-silencing transcription factor
  • REST
  • gingival fibromatosis
  • mosaic mutation
  • nonsense-mediated decay
  • whole-exome sequencing

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