RESUMEN
AXIN2 gene plays a crucial role in morphogenesis of craniofacial area and is essential for tooth development. AXIN2 gene is one of the most studied genes associated with tooth agenesis, the most common defect of dentition in humans. Polymorphic variants in AXIN2 gene are discussed in relation to the occurrence of the tooth agenesis but also as an indication of the risk of cancer. Mutations in AXIN2 gene were found in patients with colorectal or hepatocellular carcinoma, prostate cancer, ovarium or lung cancer. These findings support the hypothesis that missing teeth may be a significant marker for predisposition for cancer.
Asunto(s)
Anodoncia/genética , Proteína Axina/genética , Neoplasias/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Mutación , Polimorfismo Genético , Factores de RiesgoRESUMEN
OBJECTIVES: Tooth agenesis is one of the most common developmental anomalies in humans. Genetic and environmental factors may be of etiological importance in this condition. Among genes involved in tooth morphogenesis, mutations in PAX9, MSX1, AXIN2, WNT10a, and EDA genes have been associated with tooth agenesis. The aim of our study was to investigate the relationship between the PAX9 gene variants and tooth agenesis in the Czech population. METHODS: The selected regions of the PAX9 gene were analysed by direct sequencing and compared with the reference sequence from the GenBank online database (NCBI). RESULTS: We found several novel variants in the PAX9 gene, e.g. insertion g.5100_5101insC (rs11373281) with simultaneous substitution g.5272C>G (rs4904155) in exon 1, and mutation g.10934C>T (Gly203Gly, rs61754301) in exon 3. In subjects with full dentition we observed polymorphisms g.10276A>G (rs12882923) and g.10289A>G (rs12883049) in IVS2 (intervening sequence 2) previously related to tooth agenesis in Polish study. CONCLUSIONS: In our study we excluded a direct effect of rs12882923 and rs12883049 polymorphisms on the dental agenesis in the Czech population. All described PAX9 genetic variants were present both in patients with tooth agenesis and controls. We expect that tooth agenesis in our cohort of patients is caused by mutations in regions different from PAX9 exons analyzed in our study.
Asunto(s)
Anodoncia/genética , Factor de Transcripción PAX9/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , República Checa , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Polimorfismo Genético , Análisis de Secuencia de ADN , Población Blanca , Adulto JovenRESUMEN
Tooth agenesis is one of the most common developmental anomalies in humans. To date, many mutations involving paired box 9 (PAX9), msh homeobox 1 (MSX1), and axin 2 (AXIN2) genes have been identified. The aim of the present study was to perform screening for mutations and/or polymorphisms using the capillary sequencing method in the critical regions of PAX9 and MSX1 genes in a group of 270 individuals with tooth agenesis and in 30 healthy subjects of Czech origin. This screening revealed a previously unknown heterozygous g.9527G>T mutation in the PAX9 gene in monozygotic twins with oligodontia and three additional affected family members. The same variant was not found in healthy relatives. This mutation is located in intron 2, in the region recognized as the splice site between exon 2 and intron 2. We hypothesize that the error in pre-mRNA splicing may lead to lower expression of PAX9 protein and could have contributed to the development of tooth agenesis in the affected subjects.