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

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.

Profile evaluation of patients diagnosed with non-neoplastic proliferative lesions in a dentistry clinic

Non-neoplastic proliferative lesions (NNPLs) are alterations that affect oral mucosal tissues. The etiology of these lesions is associated with local irritant processes, principally inflammation, infections and mechanical irritants. NNPLs are classified into four groups: inflammatory fibrous hyperplasia, pyogenic granuloma, peripheral ossifying fibroma, and peripheral giant cell lesion. Aim: This cross-sectional, quantitative, retrospective, analytical, informative and educational study aimed to evaluate the profiles of patients who were diagnosed with any non-neoplastic proliferative lesion in the Unimontes Stomatology Clinic, Brazil. Methods: From January 2001 to June 2012, 1505 patients were counted who underwent anatomopathological examination, in addition to evaluations for other conditions. Results: Of these 1505 patients, 223 were diagnosed with some type of non-neoplastic proliferative lesion, and statistical analysis showed that 76% were female and 24% male and that 23.3% were between 41 and 50 years of age. Inflammatory fibrous hyperplasia was the most common NNPL (86.5%). Conclusion: Due to the high frequency of these lesions in the dental clinic, this type of survey has significant relevance for informing health professionals about these proliferative processes. This information is necessary, since the dentist is intimately involved in both the etiology, treatment and prevention of these lesions

Metachronous ameloblastic fibro-odontoma and dentigerous cyst in the posterior mandible.

An ameloblastic fibro-odontoma (AFO) is a rare mixed odontogenic tumor with histologic features of an ameloblastic fibroma in conjunction with the presence of dentin and enamel. It usually appears as a well-circumscribed radiolucency with radiopaque foci and slow growth and is commonly seen in children and young adults. A 13-year-old boy presented with an asymptomatic swelling in the posterior right region of the mandible and the right ascending ramus. The clinical, imaging, and histopathologic findings confirmed the diagnosis of an AFO. After 8 months, a radiolucent lesion involving the unerupted mandibular left third molar was observed; a final diagnosis of a dentigerous cyst (DC) was established for this lesion. Although coincidental events, metachronous odontogenic lesions suggest a possible common genetic origin, since both can be caused by related cellular signaling pathways. Complete enucleation is recommended for both AFOs and DCs; rates of recurrence are low.

Hereditary gingival fibromatosis: clinical and ultrastructural features of a new family

OBJECTIVE: This 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 DESIGN: To 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. RESULTS: Examination 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. CONCLUSIONS: This 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

Hereditary gingival fibromatosis: clinical and ultrastructural features of a new family.

OBJECTIVE: This 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 DESIGN: To 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. RESULTS: Examination 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. CONCLUSIONS: This 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.

Palate hyperpigmentation caused by prolonged use of the anti-malarial chloroquine.

The side-effects of many drugs manifest in the oral mucosa. The anti-malarial agent chloroquine diphosphate, which is also used to treat immunological, dermatological, and rheumatological disorders, usually causes pigmentary changes in the oral mucosa. This report presents a case of palate pigmentation related to the prolonged use of chloroquine diphosphate caused by the deposition of drug metabolites in the mucosa. Healthcare professionals must be aware of these drugs and their adverse effects in order to make the correct diagnosis, decide on the optimal treatment for the condition, or refer the patient to an appropriate specialist.

Effectiveness of low flow vascular lesions sclerosis with monoethanolamine: report of six cases.

Vascular malformations or even hemangiomas need therapeutic intervention if they start to cause clinical symptoms or personal discomfort. Different therapeutic modalities, including cryotherapy, corticosteroids, laser therapy, sclerotherapy, surgery, and/or embolization, can be performed successfully. Sclerotherapy with monoethanolamine is a relatively simple and effective method to treat low flow vascular lesions. We presented a report of six cases of vascular malformations treated with monoethanolamine. There were 3 male and 3 female patients, with an age range of 20 to 68 years. The patients were submitted to applications according to clinical response and/or tolerability. In all cases, low-flow vascular lesions were recorded and submitted to infiltration with 2.5% monoethanolamine, directly into the lesions. The volume applied was approximately the middle of affected area. Vascular lesions were characterized as low-flow due to absence of arterial pulsation and flat consistence. The sclerosis with 2.5% monoethanolamine resulted in complete or partial involution, without severe complications.