New evidence of genetic heterogeneity causing hereditary gingival fibromatosis and ALK and CD36 as new candidate genes.

Autor: Machado RA; Department of Oral Diagnosis, School of Dentistry, University of Campinas (FOP/UNICAMP), Piracicaba, São Paulo, Brazil.; Hospital for Rehabilitation of Craniofacial Anomalies, University of São Paulo, Bauru, São Paulo, Brazil., de Andrade RS; Department of Oral Diagnosis, School of Dentistry, University of Campinas (FOP/UNICAMP), Piracicaba, São Paulo, Brazil., Pêgo SPB; Stomatology Clinic, Dental School, State University of Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil., Krepischi ACV; Department of Genetics and Evolutionary Biology, Human Genome and Stem-Cell Research Center, Institute of Biosciences, University of São Paulo (IB/USP), São Paulo, Brazil., Coletta RD; Department of Oral Diagnosis, School of Dentistry, University of Campinas (FOP/UNICAMP), Piracicaba, São Paulo, Brazil.; Graduate Program in Oral Biology, School of Dentistry, University of Campinas, Piracicaba, São Paulo, Brazil., Martelli-Júnior H; Stomatology Clinic, Dental School, State University of Montes Claros (Unimontes), Montes Claros, Minas Gerais, Brazil.; Center for Rehabilitation of Craniofacial Anomalies, Dental School, University of José Rosario Vellano (Unifenas), Alfenas, Minas Gerais, Brazil.
Jazyk: angličtina
Zdroj: Journal of periodontology [J Periodontol] 2023 Jan; Vol. 94 (1), pp. 108-118. Date of Electronic Publication: 2022 Jul 01.
DOI: 10.1002/JPER.22-0219
Abstrakt: Background: Hereditary gingival fibromatosis (HGF) is an uncommon genetic condition characterized by slow but progressive fibrous, non-hemorrhagic, and painless growth of the gingival tissues due to the increased deposition of collagen and other macromolecules of the extracellular matrix. HGF occurs in approximately 1:750,000 individuals and can exhibit dominant or recessive inheritance. To date, five loci (2p21-p22, 2p22.3-p23.3, 4q12, 5q13-q22, and 11p15) and three genes [REST (RE1-silencing transcription factor), SOS1 (Son-of-Sevenless-1), and ZNF862 (zinc finger protein 862 gene)] have been associated with HGF. Here, our study aimed to identify genetic variants associated with HGF by applying whole-exome sequencing (WES) and bioinformatics analyses.
Methods: Thirteen Brazilian individuals with HGF and nine relatives without HGF from four unrelated families were chosen for our investigation. Blood collected from the patients and their relatives were used for WES. Five Web-available tools, namely, CADD, PolyPhen, SIFT, Mutation Taster, and Franklin's algorithms, were used to predict protein damage.
Results: WES revealed pathogenic variants affecting the known HGF genes REST (c.1491_1492delAG) and SOS1 (c.3265_3266insTAAC) in two families. Additionally, potentially pathogenic variants segregating in the other two families were mapped to ALK receptor tyrosine kinase gene (ALK) (c.361C > T) and to collagen type I receptor and thrombospondin receptor gene (CD36) (c.1133G > T).
Conclusion: Our findings reinforce the high genetic heterogeneity of HGF, identifying new variants in HGF known genes (REST and SOS1) and ALK and CD36 as new genes that cause HGF.
(© 2022 American Academy of Periodontology.)
Databáze: MEDLINE
Externí odkaz: