RESUMO
Tooth agenesis is one of the most common developmental disorders in humans. Previous studies have attributed non-syndromic tooth agenesis to mutations in several genes, including MSX1, PAX9, EDA, and AXIN2. In this study, we investigated a Chinese family with tooth agenesis combined with cleft lip. Genomic DNA was isolated from blood samples of all available family members. Candidate genes MSX1 and PAX9 were amplified by the PCR and directly sequenced. A novel heterozygous mutation at c.C565T, exon 2 of MSX1, was identified in affected members. To analyze the effect of the nonsense mutation on MSX1 expression, vectors containing wild-type and mutated MSX1 were constructed and transfected into COS7 cell lines. Real-time PCR showed that the mRNA expression of the mutated MSX1 was dramatically reduced compared with that of the wild-type MSX1. Our findings suggest that the nonsense mutation in MSX1 might have resulted in rapid degradation of the mutated transcript and caused the phenotype of tooth agenesis with cleft lip in the Chinese family.
Assuntos
Anodontia/genética , Fenda Labial/genética , Códon sem Sentido , Fator de Transcrição MSX1/genética , Fator de Transcrição PAX9/genética , Povo Asiático/genética , Estudos de Casos e Controles , China , Análise Mutacional de DNA , Feminino , Humanos , Fator de Transcrição MSX1/sangue , Fator de Transcrição MSX1/metabolismo , Masculino , Fator de Transcrição PAX9/sangue , Fator de Transcrição PAX9/metabolismo , Linhagem , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real/métodosRESUMO
OBJECTIVES: To describe the dentofacial phenotypes of three sisters with severe non-syndromic oligodontia, to report on the mutation analysis in three genes, previously shown to cause various phenotypes of non-syndromic oligodontia and in two other suspected genes. Based on the phenotypes in the pedigree of this family, the different possible patterns of transmission are discussed. METHODS: Anamnestic data and a panoramic radiograph were taken to study the phenotype of the three sisters and their first-degree relatives. Blood samples were also taken to obtain their karyotypes and DNA samples. Mutational screening was performed for the MSX1, PAX9, AXIN2, DLX1 and DLX2 genes. RESULTS: The probands' pedigree showed evidence for a recessive or multifactorial inheritance pattern. Normal chromosomal karyotypes were found and - despite the severe oligodontia present in all three sisters - no mutation appeared to be present in the five genes studied so far in these patients. CONCLUSIONS: In the three sisters reported, their common oligodontia phenotype is not caused by mutations in the coding regions of MSX1, PAX9, AXIN2, DLX1 or DLX2 genes, but genetic factors most probably play a role as all three sisters were affected. Environmental and epigenetic factors as well as genes regulating odontogenesis need further in vivo and in vitro investigation to explain the phenotypic heterogeneity and to increase our understanding of the odontogenic processes.
