REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis.

TitleREST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis.
Publication TypeJournal Article
Year of Publication2017
AuthorsBayram, Y, White, JJ, Elcioglu, N, Cho, MT, Zadeh, N, Gedikbasi, A, Palanduz, S, Ozturk, S, Cefle, K, Kasapcopur, O, Akdemir, ZCoban, Pehlivan, D, Begtrup, A, Carvalho, CMB, Paine, ISophie, Mentes, A, Bektas-Kayhan, K, Karaca, E, Jhangiani, SN, Muzny, DM, Gibbs, RA, Lupski, JR
Corporate AuthorsBaylor-Hopkins Center for Mendelian Genomics
JournalAm J Hum Genet
Date Published2017 Jul 06
KeywordsAdolescent, Base Sequence, Chromosome Segregation, Exons, Family, Female, Fibromatosis, Gingival, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Pedigree, Repressor Proteins

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.

Alternate JournalAm. J. Hum. Genet.
PubMed ID28686854
PubMed Central IDPMC5501868
Grant ListR01 NS058529 / NS / NINDS NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States