REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis.
Am J Hum Genet
; 101(1): 149-156, 2017 Jul 06.
Article
in En
| MEDLINE
| ID: mdl-28686854
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Exons
/
Genetic Predisposition to Disease
/
Fibromatosis, Gingival
/
Mutation
Type of study:
Prognostic_studies
Limits:
Adolescent
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Am J Hum Genet
Year:
2017
Type:
Article
Affiliation country:
United States