RESUMO
Tooth agenesis is a common craniofacial abnormality in humans and represents failure to develop 1 or more permanent teeth. Tooth agenesis is complex, and variations in about a dozen genes have been reported as contributing to the etiology. Here, we combined whole-exome sequencing, array-based genotyping, and linkage analysis to identify putative pathogenic variants in candidate disease genes for tooth agenesis in 10 multiplex Turkish families. Novel homozygous and heterozygous variants in LRP6, DKK1, LAMA3, and COL17A1 genes, as well as known variants in WNT10A, were identified as likely pathogenic in isolated tooth agenesis. Novel variants in KREMEN1 were identified as likely pathogenic in 2 families with suspected syndromic tooth agenesis. Variants in more than 1 gene were identified segregating with tooth agenesis in 2 families, suggesting oligogenic inheritance. Structural modeling of missense variants suggests deleterious effects to the encoded proteins. Functional analysis of an indel variant (c.3607+3_6del) in LRP6 suggested that the predicted resulting mRNA is subject to nonsense-mediated decay. Our results support a major role for WNT pathways genes in the etiology of tooth agenesis while revealing new candidate genes. Moreover, oligogenic cosegregation was suggestive for complex inheritance and potentially complex gene product interactions during development, contributing to improved understanding of the genetic etiology of familial tooth agenesis.
Assuntos
Anodontia/genética , Feminino , Ligação Genética/genética , Variação Genética/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Laminina/genética , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Masculino , Proteínas de Membrana/genética , Mutação de Sentido Incorreto/genética , Linhagem , Reação em Cadeia da Polimerase em Tempo Real , Turquia , Sequenciamento do Exoma/métodos , Proteínas Wnt/genéticaRESUMO
The intention of this study was to investigate the effect of modified 3D culture conditions on dental pulp cells (DPCs). DPCs were isolated from extracted primary molar, premolar, and wisdom teeth. Tooth samples were divided into three groups as control group; plated into methyl cellulose medium without any supplementation, growth factor (GF) group; supplemented with bone morphogenetic proteins (BMP2, BMP4), transforming growth factor—β1 (TGF—β1) and growth factor+conditioned medium (GF+CM) group; supplemented with both growth factors and pulp conditioned medium. The DPCs were tested for colony forming ability, proliferation capacity and morphology. The highest colony forming ability was detected in the GF and GF+CM groups of DPCs isolated from wisdom teeth. The proliferation capacity was higher in GF+CM group of DPCs isolated from primary molars, and in GF and GF+CM groups of DPCs isolated from wisdom teeth. Scanning electron microscope (SEM) observation of the wisdom teeth samples showed cell—cell interactions in the GF and GF+CM groups. Our results indicate that growth factors and pulp conditioned medium in methyl cellulose culture created proper environment to follow the behavior of dental cells three—dimensionally.
Assuntos
Dente Pré-Molar/citologia , Proteína Morfogenética Óssea 2/farmacologia , Comunicação Celular/fisiologia , Polpa Dentária/citologia , Dente Serotino/citologia , Fator de Crescimento Transformador beta1/farmacologia , Adolescente , Adulto , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Criança , Ensaio de Unidades Formadoras de Colônias , Humanos , Microscopia Eletrônica de Varredura , Adulto JovemRESUMO
BACKGROUND: Root fractures in permanent teeth are uncommon injuries and represent complex healing patterns. Fractures occur most often in the middle third of a root and rarely at the apical third. CASE REPORTS: Case 1: A 10- year old boy attended the Dept. Paediatric Dentistry Clinic (Istanbul University) after an accident at school 4 hrs earlier. Clinically there was a swollen upper lip, pain on the periapical region of the tooth and horizontal root fractures in the middle third of both roots of teeth 11 and 21 were noted on periapical radiography. Case 2: An 8-year old boy was involved in a bicycle accident 3 months prior to attending. A maxillary splint was present on incisor 11. Clinically an enamel-dentine crown fracture and radiographically a horizontal mid-third root fracture, were seen. Case 3: An 11-year old boy attended after a bicycle accident 1 month before, involving tooth 21. Clinically there was mobility, slight discolouration and radiographically a horizontal mid-third root. TREATMENT: In all cases only the coronal segment of roots were treated and MTA was placed as a fracture line plug. FOLLOW-UP: At 36 months follow up all teeth were asymptomatic and clinical and radiographic investigation of the teeth revealed excellent healing patterns. CONCLUSION: MTA can be considered as a good choice for a definitive root filling material in horizontal tooth root fractures with excellent biological and physical properties.