Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Animals ; Humans ; Mice ; Fibromatosis, Gingival/pathology* ; Gingiva ; Kinesins/genetics* ; Mutation/genetics* ; Phosphatidylinositol 3-Kinases/genetics*

Gingival Hyperplasia/diagnosis* ; Humans ; Immunoglobulin G ; Immunoglobulin G4-Related Disease

Humans ; Nephrotic Syndrome/therapy* ; Gingival Hyperplasia/surgery* ; Gingivectomy

Hereditary gingival fibromatosis (HGF) is a familial hereditary disease; while it is rare and usually benign, it is also characterized by the slow and progressive development of gingival tissue. This paper reports on the clinical examina-tion and history of HGF in a family of patients.
Fibromatosis, Gingival ; Gingiva ; Humans

Mucopolysaccharidosis (MPS) is an inherited metabolic disorder caused by a deficiency in enzymes that participate in the degradation of glycosaminoglycans (GAGs) such as heparin sulfate and dermatan sulfate. Left untreated, patients show progressive mental and physical deterioration due to deposition of GAGs in organs. Death often occurs due to cardiac or respiratory failure before patients reach their early twenties. MPS has several oral and dental manifestations. An enlarged head, short neck, and open mouth associated with a large tongue are major characteristics of MPS patients. Dental complications can be severe, including unerupted dentition, dentigerous cyst-like follicles, malocclusions, condylar defects, and gingival hyperplasia. A 21-year-old female patient with MPS was described in this article, with special emphasis on oral manifestations and dental treatment.
Dental Pulp Cavity ; Dentition ; Dermatan Sulfate ; Female ; Gingival Hyperplasia ; Glycosaminoglycans ; Head ; Heparin ; Humans ; Malocclusion ; Mouth ; Mucopolysaccharidoses ; Neck ; Oral Manifestations ; Respiratory Insufficiency ; Root Canal Therapy ; Tongue ; Young Adult

With the increasing number of the orthodontic patients, the relationship between periodontal and orthodontic becomes increasingly close. Orthodontic treatment can improve periodontal status, but the adverse clinical problems of periodontal tissue during orthodontic treatment are relatively common. In this paper, we discuss the problems of soft tissue, including causes, prevention, and treatment of gingivitis, gingival enlargement, gingival recession, and gingival invagination in orthodontic treatment.
Gingiva ; Gingival Overgrowth ; therapy ; Gingival Recession ; therapy ; Gingivitis ; therapy ; Humans ; Tooth Movement Techniques

Previous studies to elucidate the etiology of cyclosporine(Cs)-induced gingival overgrowth in children have not completely excluded all factors that may cause differences among individuals. This study examined the effect of cyclosporine on the metabolism of type 1 collagen(CoL-I) in experimental models that controlled the effects of biological variations on individuals. Five 5-week-old male Sprague-Dawley rats were administered Cs by gastric feeding for 6 weeks. Gingival specimens were harvested from the mandibular posterior area before beginning Cs administration and at 2, 4, and 6 weeks thereafter. Gingival fibroblasts were cultured from all the 20 biopsies collected from the gingiva. Half of the fibroblasts collected prior to the Cs administration were designated as Control. The other half of the fibroblasts were treated with Cs in vitro and called in vitro test group(Tt). The fibroblasts collected 2, 4, and 6 weeks after the Cs administration were called in vivo test groups : T2, T4, T6, respectively. Immunofluorescence microscopy was used to detect CoL-I in all the fibroblasts. CoL-I was analyzed at both the gene and protein expression levels by real-time polymerase chain reaction and western blotting. Changes in CoL-I before and after Cs treatment were evaluated from the gingiva of each rat. There was no significant difference in gene expression of CoL-I in the control and test groups. CoL-I protein expression levels of fibroblasts increased in in vitro Cs treatment for each individual, and also increased in in vivo Cs treatment. In this study, the experimental method that control biological variations that can occur due to differences among individuals was useful. Subsequent studies on other factors besides CoL-I and in-depth studies in humans are needed.
Animals ; Biopsy ; Blotting, Western ; Child ; Collagen Type I ; Cyclosporine ; Fibroblasts ; Gene Expression ; Gingiva ; Gingival Overgrowth ; Humans ; In Vitro Techniques ; Male ; Metabolism ; Methods ; Microscopy, Fluorescence ; Models, Theoretical ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

Anticonvulsants, calcium channel blockers and immunosuppressants are representative drugs related with gingival enlargement. Clinical signs and symptoms caused by drug-induced gingival enlargment frequently appear within 1 to 3 months after medication. At initial stage, it is limited to attached gingiva but may extend coronally and interfere with esthetics, mastication and speech. Interproximal spaces are common beginning area and pathologic teeth migration could be occurred by the lesion. Withdrawal or substitution of medication would be the most effective treatment of drug-induced gingival enlargement. However, periodontal treatment and further supportive periodontal therapy should be provided where change in medication is impossible. The present study reports the cases which show the resolution of inflammation with spontaneous teeth migration without change in medication. In all cases discussed in this report could be efficiently managed with proper periodontal treatment and further supportive periodontal therapy.
Anticonvulsants ; Calcium Channel Blockers ; Esthetics ; Gingiva ; Gingival Overgrowth ; Humans ; Immunosuppressive Agents ; Inflammation ; Mastication ; Periodontal Diseases ; Tooth*

Drug-induced gingival overgrowth (DIGO) is characterized by fibrous gingival hyperplasia and increased gingival volume. DIGO is histologically associated with proliferation of cells and deposition of extracellular matrices, particularly collagen. Integrin α2β1 is related to collagen phagocytosis and involved in the occurrence and progression of DIGO. This paper reviews the progress of research on the relationship between integrin α2β1 and DIGO.
Collagen ; Gingiva ; Gingival Overgrowth ; Humans ; Integrin alpha2beta1 ; Phagocytosis

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.
Amelogenesis Imperfecta* ; Amelogenesis* ; Cone-Beam Computed Tomography ; Dental Enamel Hypoplasia ; Dental Enamel* ; Dentists ; Fibromatosis, Gingival ; Humans ; Kidney Diseases ; Male ; Metabolic Diseases ; Nephrocalcinosis ; Nephrolithiasis* ; Phenotype ; Radiography ; Tooth ; Young Adult