OBJECTIVE: To explore potential pathogenic processes and possible treatments using unbiased and reliable bioinformatic tools.
METHODS: Gene expression profiles of control and hepatocyte growth factor (HGF) samples were downloaded from CNP0000995. Analysis of differentially expressed genes (DEGs) was conducted using R software (version 4.2.1, R Foundation, Vienna, Austria). Functional enrichment analyses were performed using the Gene Ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) databases, then the proteinprotein interaction (PPI) network was constructed to screen the top 10 hub genes. Finally, five genes related to cell junctions were selected to build gene-miRNA interactions and predict small-molecule drugs.
RESULTS: A total of 342 downregulated genes and 188 upregulated genes were detected. Candidate pathways include the extracellular matrix (ECM) receptor interaction pathway, the TGF-β signalling pathway and the cell adhesion molecule (CAM) pathway, which were discovered through KEGG and GSEA enrichment studies. GO analyses revealed that these DEGs were significantly enriched in cell adhesion, the adherens junction and focal adhesion. Five hub genes (CDH1, SNAP25, RAC2, APOE and ITGB4) associated with cell adhesion were identified through PPI analysis. Finally, the gene-miRNA regulatory network identified three target miRNAs: hsa-miR-7110-5p, hsa-miR-149-3p and hsa-miR-1207-5p. Based on the gene expression profile, the small-molecule drugs zebularine, ecuronium and prostratin were selected for their demonstrated binding activity when docked with the mentioned molecules.
CONCLUSIONS: This study offered some novel insights into molecular pathways and identified five hub genes associated with cell adhesion. Based on these hub genes, three potential therapeutic miRNAs and small-molecule drugs were predicted, which are expected to provide guidance for the treatment of patients with HGF.

OBJECTIVE: The purpose of this study was to present the use of computer-assisted periodontal surgery utilizing a novel surgical guide for cases with severe gingival enlargement through a clinical application in a patient with hereditary gingival fibromatosis.
METHODS: The treatment plan included nonsurgical periodontal therapy, surgical periodontal treatment, and regular periodontal maintenance before the initiation of orthodontic treatment. Due to the increased soft tissue thickness, a surgical guide with a novel design was fabricated to facilitate the periodontal surgery since most of the patient\'s teeth were malpositioned and underexposed due to fibromatosis. For this purpose, the patient\'s intraoral scan was merged with a CBCT image in order to plan surgical excisions based on the anatomy of the teeth and the bone contour.
RESULTS: The customized surgical guide facilitated the gingivectomy by controlling not only the shape of the initial incisions but also their orientation toward the level of the cementoenamel junction, improving the efficiency of the clinical time compared with freehand surgery and assisting in the verification of the final soft tissue shape, based on the treatment plan.
CONCLUSIONS: Digital technology through the superimposition of multiple data sets can assist in the diagnosis and multidisciplinary management of cases with gingival fibromatosis. The proposed design of the surgical guide can facilitate soft tissue surgery based on the digital treatment plan, leading to more predictable management of the soft tissue, especially in patients with severe gingival enlargement, as in cases with hereditary gingival fibromatosis or drug-induced gingival overgrowth.

Hereditary gingival fibromatosis (HGF) is an uncommon slow-growing fibrous overgrowth characterized by connective tissue accumulation. It presents as an isolated feature or as a manifestation of any syndrome. Various syndromes associated with HGF are inherited by autosomal dominant/recessive/X-linked traits. Zimmermann-Laband syndrome (ZLS) is a rare, autosomal dominant inherited disease manifested with gingival fibromatosis (GF), nose and ears abnormalities, and hypoplastic/dysplastic nails or terminal phalanges of hand and feet. Although the pattern of inheritance was found to be both autosomal dominant and recessive traits, the molecular basis is still unclear. This report presents a possible case of ZLS-associated HGF in a 25-year-old female patient who presents with GF, hypertrichosis, and other syndrome-related features. Her father was similarly affected whereas her mother and sibling were asymptomatic. The patient and her family members were explained about the condition and surgical periodontal therapy was carried out for the patient to improve esthetics and was followed up regularly. Esthetics was significantly improved and no recurrence was noted at the end of 6 months.

OBJECTIVE: The objective of this study was to detect the undiscovered bioinformatics information about hereditary gingival fibromatosis and find focuses from published datasets.
METHODS: Two published datasets containing gingival tissue expression profiles of HGF and healthy groups were collected from GEO database. GSE4250 was utilized for cardinality analysis, including the differentially expressed gene analysis, enrichment analyses, hierarchical clustering analysis, and protein-protein interaction network. Key genes were obtained from the protein interaction network plot. GSE58482 was utilized for validation.
RESULTS: Analysis of the expression profiling by array, there were 785 genes (380 upregulated genes, 405 downregulated genes) expressed differentially between HGF gingival tissue and healthy gingival tissue. KEGG and GO enrichment analyses obtained candidate pathways. Differentially expressed genes were associated with activated pathways like skin barrier pathway and cornified envelope pathway. Repressed pathways included ion homeostasis pathway, receptor ligand activity pathway, and cell population proliferation pathway. Key genes such as F2R, TGM7, and MMP13 were confirmed with differential expression by external validation.
CONCLUSIONS: By bioinformatics approaches, we found new discoveries including several pathways and key genes. These discoveries deserve attention and research in the future.

Hereditary gingival fibromatosis (HGF) is an uncommon condition characterized by a benign, local, or diffuse gingival overgrowth. It may cover the teeth partially or totally, causing essential aesthetic, phonetic, and masticatory disorders. In this report, we discuss a case of an 11-year-old boy who presented with severe gingival enlargement. The diagnosis of HGF was made based on clinical examination and family history, with two of the patient\'s brothers and his paternal aunt being affected with the same disease. The patient was managed with electrosurgery under general anesthesia.

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.

BACKGROUND: Hereditary 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.
CONCLUSIONS: The 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.

Hereditary gingival fibromatosis (HGF) is a proliferative fibrous lesion causing severe gingival enlargement, affecting the esthetics, as well as posing various periodontal problems. This case report addresses the diagnosis and treatment of one such rare case of HGF where the patient presented with generalized diffuse gingival enlargement involving the maxillary and mandibular arches extending on the buccal and lingual/palatal surfaces and covering the incisal/occlusal third of the tooth, resulting in altered esthetics, difficulty in speech, and mastication. Gingivectomy was carried out in all the four quadrants using diode laser. The healing was uneventful; the patient was satisfied with her esthetics and was able to resume her oral hygiene practices. Even though recurrence cannot be predicted, the risk of recurrence can be outweighed with the psychological and functional benefits. Long-term follow-up will be required to evaluate the predictability of the different surgical techniques.

OBJECTIVE: Hereditary gingival fibromatosis (HGF) is an uncommon, inherited condition with slow and progressive fibrous hyperplasia of the gingiva. Due to its association with mastication, speech, and occlusion problems, early diagnosis is important. We sought to summarize the available data regarding the epidemiology, clinical characteristics, and outcomes of children with HGF (< 18 years).
METHODS: A systematic literature review of the MEDLINE and Cochrane Library databases was conducted with respect to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (end-of-search date: March 1, 2019).
RESULTS: A total of 99 articles reporting on 146 patients were included. The mean age was 10.82 ± 3.93 years, and generalized gingival enlargement was seen in 97.16% (95% CI 92.69 to 99.14). Jaw, gingival, and teeth abnormalities; poor oral hygiene; eating; or speech difficulties were typical HGF-induced, while 60.90% had extraoral manifestations (95% CI 52.41 to 68.78). The disease was most commonly inherited in an autosomal dominant manner (88.41%, 95% CI 78.5 to 94.26), and about one-third of the patients had syndromic HGF (33.85%, 95% CI 23.50 to 46.00). Gingivectomy was performed in the majority of cases (91.15%, 95% CI 84.31 to 95.29), and recurrence was seen in 33.85% (95% CI 23.50 to 46.00).
CONCLUSIONS: HGF should be suspected in children with nodularity and gingival fibrosis, teeth abnormalities, or jaw distortion. Family history can help to establish the diagnosis.
CONCLUSIONS: More cases should focus on longer-term follow-up after gingivectomy as disease recurrence is not uncommon.

Hereditary gingival fibromatosis (HGF) is a rare condition affecting the gingiva and may or may not be a clinical feature of other syndromes. It has been classified as a nondental biofilm-induced gingival disease. The pathogenesis of this condition has been poorly understood till date. Although different genetic mutations have been implicated to play a role, there is considerable interest on an addition mutation of Son of Sevenless-1 (SOS-1) gene. We report a case of a 27-year-old male patient who came to us with the complaint of enlarged gums of several years\' duration. There were other members in his family who were similarly affected. After the clinical diagnosis of HGF was confirmed, the patient and his available family members were subjected to a genetic analysis for identification of mutation in SOS-1 gene, which turned out to be negative. The patient was treated with nonsurgical periodontal therapy and is under regular follow-up. To the best of our knowledge, this is the first study to assess SOS-1 mutation in an Indian family.