%0 Journal Article %J Am J Hum Genet %D 2017 %T REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis. %A Bayram, Yavuz %A White, Janson J %A Elcioglu, Nursel %A Cho, Megan T %A Zadeh, Neda %A Gedikbasi, Asuman %A Palanduz, Sukru %A Ozturk, Sukru %A Cefle, Kivanc %A Kasapcopur, Ozgur %A Coban Akdemir, Zeynep %A Pehlivan, Davut %A Begtrup, Amber %A Carvalho, Claudia M B %A Paine, Ingrid Sophie %A Mentes, Ali %A Bektas-Kayhan, Kivanc %A Karaca, Ender %A Jhangiani, Shalini N %A Muzny, Donna M %A Gibbs, Richard A %A Lupski, James R %K Adolescent %K Base Sequence %K Chromosome Segregation %K Exons %K Family %K Female %K Fibromatosis, Gingival %K Genetic Predisposition to Disease %K Humans %K Male %K Middle Aged %K Mutation %K Pedigree %K Repressor Proteins %X

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.

%B Am J Hum Genet %V 101 %P 149-156 %8 2017 Jul 06 %G eng %N 1 %1 https://www.ncbi.nlm.nih.gov/pubmed/28686854?dopt=Abstract %R 10.1016/j.ajhg.2017.06.006