Exomic and transcriptomic alterations of hereditary gingival fibromatosis.
Oral Dis
; 25(5): 1374-1383, 2019 Jul.
Article
em En
| MEDLINE
| ID: mdl-30907493
ABSTRACT
OBJECTIVE:
Hereditary gingival fibromatosis (HGF) is a rare oral disease characterized by either localized or generalized gradual, benign, non-hemorrhagic enlargement of gingivae. Although several genetic causes of HGF are known, the genetic etiology of HGF as a non-syndromic and idiopathic entity remains uncertain. SUBJECTS ANDMETHODS:
We performed exome and RNA-seq of idiopathic HGF patients and controls, and then devised a computational framework that specifies exomic/transcriptomic alterations interconnected by a regulatory network to unravel genetic etiology of HGF. Moreover, given the lack of animal model or large-scale cohort data of HGF, we developed a strategy to cross-check their clinical relevance through in silico gene-phenotype mapping with biomedical literature mining and semantic analysis of disease phenotype similarities.RESULTS:
Exomic variants and differentially expressed genes of HGF were connected by members of TGF-ß/SMAD signaling pathway and craniofacial development processes, accounting for the molecular mechanism of fibroblast overgrowth mimicking HGF. Our cross-check supports that genes derived from the regulatory network analysis have pathogenic roles in fibromatosis-related diseases.CONCLUSIONS:
The computational approach of connecting exomic and transcriptomic alterations through regulatory networks is applicable in the clinical interpretation of genetic variants in HGF patients.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcriptoma
/
Exoma
/
Fibromatose Gengival
Limite:
Humans
Idioma:
En
Revista:
Oral Dis
Assunto da revista:
ODONTOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article