RESUMO
OBJECTIVE: To examine the histomorphologic and histomorphometric features of tissue from 3 unrelated families with hereditary gingival fibromatosis (HGF). STUDY DESIGN: Twelve affected individuals from 3 HGF families and 3 control subjects were evaluated. Gingival samples were fixed in formalin and embedded in paraffin for hematoxylin and eosin stain to count the number of fibroblast and inflammatory cells. Sirius red staining was performed to quantitate the amount of collagen present. RESULTS: Histomorphologic analysis of HGF showed extension of epithelial rete ridges into the underlying lamina propria and the presence of collagen bundles in the connective tissue. Analysis of the mean area fraction of collagen showed that there were significant increases in the collagen fraction for all HGF types compared with control subjects (P < .05). There were significant increases in the number of fibroblasts for HGFa and HGFb compared with control subjects (P < .05). The number of fibroblasts for HGFc were similar to that for control subjects. CONCLUSIONS: The collagen fraction was significantly greater in all HGF types compared with controls. The number of fibroblasts was significantly increased in 2 of the 3 HGF types compared with controls. These data indicate that different mechanisms may be responsible for tissue enlargement in different forms of HGF.
Assuntos
Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Gengiva/patologia , Adolescente , Adulto , Estudos de Casos e Controles , Contagem de Células , Criança , Colágeno/análise , Células Epiteliais/patologia , Feminino , Fibroblastos/patologia , Fibromatose Gengival/classificação , Heterogeneidade Genética , Humanos , Processamento de Imagem Assistida por Computador , Inflamação/patologia , Masculino , Mucosa/patologiaRESUMO
La presencia de deformidades mucogingivales generalmente tiene un impacto en cuanto se refiere a la estética y función, la variedad de presentaciones de estas deformidades impide hacer una única definición. Las deformidades mucogingivales como se define aqui, puede ser congénita, del desarrollo o por inducción farmacológica. Estas pueden ocurrir alrededor de piezas dentarias naturales o de implantes, pueden localizarse en tejidos blandos o ser asociados con defectos de la estructura ósea. Pueden también mostrar diferentes grados de severidad o extensión. Cualquier clasificación de deformidades mucogingivales deberán incluir un método de identificación de las diferentes condiciones que incluyan un buen diagnóstico, identificación etiológica, investigación y el tratamiento adecuado además de su evolución posterior. Este es el reporte de un caso familiar de cuatro hermanas que presentaron y presentan la enfermedad, cuyas evidencias clínicas y la historia de la enfermedad familiar hacen pensar en una fibromatosis gingival hereditaria, asociadas a la no erupción de piezas dentarias, especialmente premolares superiores e inferiores que han provocado la formación de quistes dentigeros, además de un probable hirsutismo.
Assuntos
Adolescente , Humanos , Fibromatose Gengival , Fibromatose Gengival/classificação , Fibromatose Gengival/diagnóstico por imagem , Fibromatose Gengival/etiologia , Fibromatose Gengival/patologiaRESUMO
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.
Assuntos
Fibromatose Gengival/classificação , Fibromatose Gengival/genética , Ligação Genética/genética , Mutação/genética , Proteína SOS1/genética , Sequência de Aminoácidos , Sequência de Bases , Western Blotting , Brasil , Cromossomos Humanos Par 2/genética , Análise Mutacional de DNA , Éxons/genética , Feminino , Genes Dominantes/genética , Humanos , Íntrons/genética , Escore Lod , Masculino , Dados de Sequência Molecular , Linhagem , Mapeamento Físico do Cromossomo , Estrutura Terciária de Proteína , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteína SOS1/químicaRESUMO
OBJECTIVE: The purpose of this study was to analyze the ultrastructure of gingival connective tissue from patients in one family affected by hereditary gingival fibromatosis (HGF). STUDY DESIGN: Electron microscopic examination was performed with gingival tissue from 10 patients from a Brazilian family with 132 members. Fifty of 96 persons at risk for this disorder were affected, which is consistent with an autosomal dominant pattern of inheritance. RESULTS: The extracellular matrix showed flocculent material and collagen fibrils with structural abnormalities and variation in diameter. Increased numbers of oxytalan fibers were identified; however, elastic fibers were rare in the analyzed areas. CONCLUSIONS: The structural alterations found in HGF appear similar to those described in certain other heritable collagen disorders, suggesting that HGF should be included in the group of hereditary diseases in which connective tissue alterations have a distinct pattern, in contrast to reactive fibrotic gingival enlargements with no genetic component.