RESUMO
Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (ANTXR2) located on chromosome 4q21. Characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. The present report describes a pair of sibs and three other JHF/ISH patients whose diagnoses were based on typical clinical manifestations and confirmed by histopathologic analyses and/or molecular analysis. A comparison of ISH and JHF, additional thoughts about new terminology (hyaline fibromatosis syndrome) and a modified grading system are also included.
Assuntos
Doenças do Tecido Conjuntivo/genética , Síndrome da Fibromatose Hialina/genética , Síndrome da Fibromatose Hialina/patologia , Proteínas de Membrana/genética , Criança , Pré-Escolar , Doenças do Tecido Conjuntivo/patologia , Doenças do Tecido Conjuntivo/cirurgia , Feminino , Fibromatose Gengival/genética , Fibromatose Gengival/patologia , Hiperplasia Gengival/genética , Hiperplasia Gengival/patologia , Humanos , Síndrome da Fibromatose Hialina/cirurgia , Masculino , Receptores de Peptídeos , Adulto JovemRESUMO
PURPOSE: Papilion-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder that involves palmoplantar keratosis (PK) and severe aggressive periodontitis. Cathepsin C (CTSC) gene mutations are etiologic for PLS, with more than 60 different mutations reported in different ethnic groups worldwide. The purpose of this study was to report a novel cathepsin C mutation in a Brazilian patient. METHODS: A 4-year-old boy presented with aggressive periodontitis, recession, missing teeth, and hyperkeratosis of the palms of hands and soles. Peripheral blood samples were obtained from family members for genomic DNA isolation. The coding region and exon/intron boundaries of the CTSC gene were amplified and sequenced. RESULTS: The patient had a PLS phenotype, which included PK and early-onset severe periodontitis. Sequence analysis showed a novel CTSC mutation (c.267-268del) present in the homozygous state. CONCLUSION: This report described a novel mutation in a family with Brazilian Papillon-Lefèvre syndrome and presented a review of all cathepsin C (65) mutations reported to date.
Assuntos
Catepsina C/genética , Doença de Papillon-Lefevre/genética , Brasil , Pré-Escolar , Consanguinidade , Humanos , Masculino , Mutação , Doença de Papillon-Lefevre/enzimologia , Linhagem , FenótipoRESUMO
Amelogenesis imperfecta (AI) is a genetically heterogeneous group of diseases that result in defective development of tooth enamel. Mutations in several enamel proteins and proteinases have been associated with AI. The object of this study was to evaluate evidence of etiology for the six major candidate gene loci in two Brazilian families with AI. Genomic DNA was obtained from family members and all exons and exon-intron boundaries of the ENAM, AMBN, AMELX, MMP20, KLK4 and Amelotin gene were amplified and sequenced. Each family was also evaluated for linkage to chromosome regions known to contain genes important in enamel development. The present study indicates that the AI in these two families is not caused by any of the known loci for AI or any of the major candidate genes proposed in the literature. These findings indicate extensive genetic heterogeneity for non-syndromic AI.
Assuntos
Amelogênese Imperfeita/genética , Amelogênese/genética , DNA/genética , Proteínas do Esmalte Dentário/genética , Esmalte Dentário/crescimento & desenvolvimento , Mutação , Amelogênese Imperfeita/epidemiologia , Amelogênese Imperfeita/metabolismo , Brasil/epidemiologia , Proteínas do Esmalte Dentário/metabolismo , Éxons , Família , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Incidência , Masculino , LinhagemRESUMO
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
Estudos epidemiológicos têm demonstrado que a prevalência de cárie e doença periodontal ainda é elevada em alguns países em desenvolvimento, embora mostre uma tendência geral de declínio. Nestes países o tratamento para doença periodontal avançada e cárie dental é ainda a extração do dente. O objetivo do presente estudo foi determinar a prevalência de dentes ausentes em uma população de adolescentes e adultos jovens. A população estudada compreendeu 321 indivíduos que procuraram tratamento dentário na Clínica Odontológica da Universidade de Taubaté, em Taubaté, estado de São Paulo. Os participantes do estudo tinham entre 15 e 25 anos de idade (19.51 ± 3.21), e pertenciam a 3 grupos étnicos: Negro, Branco e Pardo. Foram conduzidas entrevistas afim de se determinar a história média e hábito de fumar dos participantes. Indivíduos com problemas sistêmicos sem acompanhamento médico regular foram excluídos deste estudo. O exame bucal completo foi conduzido por um único examinador, e a perda dentária foi registrada para cada participante