IADR Abstract Archives
Dentinogenesis Imperfecta Type-II – Genotype and Phenotype Analyses in Three Danish Families
Objectives: Dentinogenesis imperfecta (DI) is a rare debilitating hereditary disorder affecting dentin formation and causing loss of the overlying enamel. DI has an estimated incidence of 1:8000 and can be classified into three subgroups: DI-I, DI-II, and DI-III. The aim of the present study was to investigate genotype-phenotype findings in three families with DI-II with special reference to mutations in the DSPP gene and clinical, histological and imaging manifestations.
Methods: 9 patients from three unrelated families participated in the study. The families have been examined longitudinally and patient age ranged from 3-55 years. Clinical and radiographic examinations had been performed, and the dental status was documented using photographic images.
Four extracted and decalcified tooth samples were prepared for histological analysis to assess dysplastic manifestations in the dentin and an optical coherence tomography was applied to evaluate the degree of mineralization in vivo. Buccal swab samples were collected from all participants and extracted for genomic DNA. A linkage analysis of five polymorphic markers flanking the DSPP gene was used to genotype the families while the effect of the mutations on the function and structure of the DSPP gene was analyzed with bioinformatics software programs.
Results: The clinical and radiographic disturbances in the permanent dentition indicated interfamilial variability in DI-II manifestations providing a possible molecular explanation to the differences in phenotypic features. The histological analysis revealed dysplastic changes in the dentin and the tomographic imaging revealed delineated areas of hypomineralization in the enamel adjacent to the dentino-enamel junction. Direct DNA sequence analysis identified three distinct mutations, one of which was novel.
Conclusions: The molecular pathogenesis by which the DSPP mutations have caused DI-II indicates genotype-phenotype correlation and may explain the interfamilial variability in phenotypic features. The presented data also indicate that DI-II might affect the ectodermal structures, but further studies are needed to confirm this.
Methods: 9 patients from three unrelated families participated in the study. The families have been examined longitudinally and patient age ranged from 3-55 years. Clinical and radiographic examinations had been performed, and the dental status was documented using photographic images.
Four extracted and decalcified tooth samples were prepared for histological analysis to assess dysplastic manifestations in the dentin and an optical coherence tomography was applied to evaluate the degree of mineralization in vivo. Buccal swab samples were collected from all participants and extracted for genomic DNA. A linkage analysis of five polymorphic markers flanking the DSPP gene was used to genotype the families while the effect of the mutations on the function and structure of the DSPP gene was analyzed with bioinformatics software programs.
Results: The clinical and radiographic disturbances in the permanent dentition indicated interfamilial variability in DI-II manifestations providing a possible molecular explanation to the differences in phenotypic features. The histological analysis revealed dysplastic changes in the dentin and the tomographic imaging revealed delineated areas of hypomineralization in the enamel adjacent to the dentino-enamel junction. Direct DNA sequence analysis identified three distinct mutations, one of which was novel.
Conclusions: The molecular pathogenesis by which the DSPP mutations have caused DI-II indicates genotype-phenotype correlation and may explain the interfamilial variability in phenotypic features. The presented data also indicate that DI-II might affect the ectodermal structures, but further studies are needed to confirm this.