Case Report: A Case of Hereditary Gingival Fibromatosis With a High Level of Human β Defensins in Gingival Epithelium
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ABSTRACT:
SUBMITTER: Gao G
PROVIDER: S-EPMC8594454 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHereditary gingival fibromatosis (HGF) is a rare condition characterized by slowly progressive overgrowth of the gingiva. The severity of overgrowth may differ from mild causing phonetic and masticatory issues, to severe resulting in diastemas or malposition of teeth. Both, autosomal-dominant and autosomal-recessive forms of HGF are described. The aim of this review is a clinical overview, as well as a summary and discussion of the involvement of candidate chromosomal regions, pathogenic variants of genes, and candidate genes in the pathogenesis of HGF. The loci related to non-syndromic HGF have been identified on chromosome 2 (GINGF, GINGF3), chromosome 5 (GINGF2), chromosome 11 (GINGF4), and 4 (GINGF5). Of these loci, pathogenic variants of the SOS-1 and REST genes inducing HGF have been identified in the GINGF and the GINGF5, respectively. Furthermore, among the top 10 clusters of genes ranked by enrichment score, ATP binding, and fibronectin encoding genes were proposed as related to HGF.ConclusionThe analysis of clinical reports as well as translational genetic studies published since the late'90s indicate the clinical and genetic heterogeneity of non-syndromic HGF and point out the importance of genetic studies and bioinformatics of more numerous unrelated families to identify novel pathogenic variants potentially inducing HGF. This strategy will help to unravel the molecular mechanisms as well as uncover specific targets for novel and less invasive therapies of this rare, orphan condition.
| S-EPMC8611899 | biostudies-literature
Project description:Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis which is featured as a localized or generalized overgrowth of gingivae. Currently two genes (SOS1 and REST), as well as four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15), have been identified as associated with HGF in a dominant inheritance pattern. Here, we report 13 individuals with autosomal-dominant HGF from a four-generation Chinese family. Whole-exome sequencing followed by further genetic co-segregation analysis was performed for the family members across three generations. A novel heterozygous missense mutation (c.2812G > A) in zinc finger protein 862 gene (ZNF862) was identified, and it is absent among the population as per the Genome Aggregation Database. The functional study supports a biological role of ZNF862 for increasing the profibrotic factors particularly COL1A1 synthesis and hence resulting in HGF. Here, for the first time we identify the physiological role of ZNF862 for the association with the HGF.
| S-EPMC8856651 | biostudies-literature
Project description: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.
| S-EPMC5501868 | biostudies-literature
Project description:Hereditary gingival fibromatosis (HGF) is a rare, clinically variable disorder characterized by slowly progressive fibrous overgrowth of the gingiva. Four gene loci have been mapped for autosomal dominant non-syndromic HGF (adHGF). The molecular basis of adHGF remains largely unknown, with only a single SOS1 gene mutation identified so far at the gingival fibromatosis 1 (GINGF1) locus in one family. We identified an adHGF family with ten affected individuals in whom onset of gingival fibromatosis concurred with the eruption of the primary teeth. In order to identify the molecular basis in this family, we tested for linkage of the disease to known adHGF loci. A maximal multipoint logarithm of the odds score of 3.91 was obtained with marker D2S390 (theta = 0) at the GINGF3 locus on chromosome 2p23.3-p22.3, and linkage to other known loci was excluded. Sequencing two candidate genes, ALK and C2orf18, and a single nucleotide polymorphisms array analysis did not reveal a mutation or copy number variation in a patient from the family. We refined the GINGF3 locus to a 6.56-cM, 8.27-Mb region containing 112 known and hypothetical genes, and our data and a search of the literature suggest that GINGF3 is a major adHGF locus.
| S-EPMC2812425 | biostudies-literature
Project description:Gingival fibromatosis is characterized by a slowly progressive benign enlargement of the oral gingival tissues. The condition results in the teeth being partially or totally engulfed by keratinized gingiva, causing aesthetic and functional problems. Both genetic and pharmacologically induced forms of gingival fibromatosis are known. The most common genetic form, hereditary gingival fibromatosis (HGF), is usually transmitted as an autosomal dominant trait, although sporadic cases are common and autosomal recessive inheritance has been reported. The genetic basis of gingival fibromatosis is unknown. We identified an extended family (n=32) segregating an autosomal dominant form of isolated gingival fibromatosis. Using a genomewide search strategy, we identified genetic linkage (Zmax=5.05, straight theta=.00) for the HGF phenotype to polymorphic markers in the genetic region of chromosome 2p21 bounded by the loci D2S1788 and D2S441. This is the first report of linkage for isolated HGF, and the findings have implications for identification of the underlying genetic basis of gingival fibromatosis.
| S-EPMC1377037 | biostudies-literature
Project description:To identify dysregulated genes in HGF (Hereditary Gingival Fibromatosis) patients, expression profiling was performed using Affymetrix Human Genome U133 plus 2.0 arrays. Total RNA was extracted from gingival tissue specimens excised from two non-syndromic HGF patients, siblings in one family, and three normal controls. Quantity and integrity of the total RNA was measured and assessed by Nanodrop spectrophotometer (Thermo Fisher Scientific) and agarose gel electrophoresis. In brief, cDNA preparation, cRNA labeling, hybridization to Affymetrix Human Genome U133 plus 2.0 arrays, and chip scanning were performed in accordance with the manufacturer’s protocol (Affymetrix). *.CEL data from the raw chip scans were imported into the Partek GS 6.5 and normalized by RMA normalization algorithms. Comparisons between the HGF and control group were performed with one-way ANOVA (p≤0.05).
2019-12-31 | E-MTAB-7801 | biostudies-arrayexpress
Project description:Hereditary gingival fibromatosis (HGF) is a benign, non-hemorrhagic and fibrous gingival overgrowth that may cover all or part of the teeth. It typically interferes with speech, lip closure and chewing, and can also be a psychological burden that affects the self-esteem of patients. Owing to high genetic heterogeneity, genetic testing to confirm diagnosis is not justified. It is therefore important to identify key signature genes and to understand the molecular mechanisms underlying HGF. The aim of the present study was to determine HGF-related genes and to analyze these genes through bioinformatics methods. A total of 249 differentially expressed genes (DEGs), consisting of 65 upregulated and 184 downregulated genes, were identified in the GSE4250 dataset of Gene Expression Omnibus (GEO) when comparing with the gums of HGF patients with those of healthy controls using the affy and limma packages in R. Subsequently, 28 enriched gene ontology terms were obtained from the Database for Annotation, Visualization and Integrated Discovery, and a protein-protein interaction (PPI) network was constructed and analyzed using STRING and Cytoscape. There were 99 nodes and 118 edges in the PPI network of these DEGs obtained through STRING. Among these nodes, 12 core genes were identified, of which the highest degree node was the gene for POTE ankyrin domain family member I. Collectively the results indicate that bioinformatics methods may provide effective strategies for predicting HGF-related genes and for understanding the molecular mechanisms of HGF.
| S-EPMC5776408 | biostudies-literature
Project description:Cherubism is an inherited, autosomal dominant disorder that characteristically affects the jaws of children. The disease typically manifest as a bilateral swelling with associated submandibular lymph node enlargements and usually regresses as age advances. The disease is microscopically indistinguishable from other giant cell lesions and is essentially a clinical diagnosis. The association of cherubism with gingival fibromatosis, epilepsy, mental retardation, stunted growth, and hypertrichosis is referred as Ramon syndrome. We report a case of Ramon syndrome in an 8 year old girl.
| S-EPMC2878617 | biostudies-literature
Project description:ObjectiveThis article describes the diagnosis, clinical and microscopic (histopathology and ultrastructural) features and treatment of a new family with hereditary gingival fibromatosis (HGF) and highlights the importance of this genetic condition.Study designTo characterize the pattern of inheritance and the clinical features, members of a new family with HGF were examined. The pedigree was reliably constructed including the four latest generations of family. Hematoxylin and eosin staining and ultrastructural analysis were performed with the gingival tissue.ResultsExamination of the family pedigree revealed that the patient III-2 represent the index patient of this family (initial patient with a mutation), which was transmitted to her daughter through an autosomal dominant mode of inheritance. The affected patients showed a generalized gingival overgrowth. The patient was treated with surgical procedures of gingivectomy and gingivoplasty. The diagnosis was confirmed by histopathology examination that showed a well-structured epithelium with elongated and thin papillae inserted in fibrous connective tissue with increased amount of collagen. The ultrastructural aspects of the tissue show collagen fibrils exhibiting their typically repeating banding pattern with some fibrils displaying loops at their end. Moreover, it was possible to seen in some regions fibrillar component presenting tortuous aspects and loss of the alignment among them.ConclusionsThis HGF frequently resulted in both esthetic and functional problems. The genetic pattern of this Brazilian family suggested a new mutation, which was later transmitted by an autosomal dominant trait.
| S-EPMC4393976 | biostudies-literature
Project description:Hereditary gingival fibromatosis (HGF) is a rare, autosomal dominant form of gingival overgrowth. Affected individuals have a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of the oral masticatory mucosa. Genetic loci for autosomal dominant forms of HGF have been localized to chromosome 2p21-p22 (HGF1) and chromosome 5q13-q22 (HGF2). To identify the gene responsible for HGF1, we extended genetic linkage studies to refine the chromosome 2p21-p22 candidate interval to approximately 2.3 Mb. Development of an integrated physical and genetic map of the interval identified 16 genes. Sequencing of these genes, in affected and unaffected HGF1 family members, identified a mutation in the Son of sevenless-1 (SOS1) gene in affected individuals. In this report, we describe the genomic structure of the SOS1 gene and present evidence that insertion of a cytosine between nucleotides 126,142 and 126,143 in codon 1083 of the SOS1 gene is responsible for HGF1. This insertion mutation, which segregates in a dominant manner over four generations, introduces a frameshift and creates a premature stop codon, abolishing four functionally important proline-rich SH3 binding domains normally present in the carboxyl-terminal region of the SOS1 protein. The resultant protein chimera contains the wild-type SOS1 protein for the N-terminal amino acids 1-1083 fused to a novel 22-amino acid carboxyl terminus. Similar SOS1 deletion constructs are functional in animal models, and a transgenic mouse construct with a comparable SOS1 chimera produces a phenotype with skin hypertrophy. Clarification of the functional role of this SOS1 mutant has implications for understanding other forms of gingival fibromatosis and corrective gingival-tissue management.
| S-EPMC379122 | biostudies-literature