Abstract for presentation at 11th International Congress of Human Genetics

Clinical features and molecular basis for hereditary disorders related to the teeth formation; diagnosis of three families with different diseases

  • MIyuki Kida, Department of Pediatrics,Hokkaido University Graduate School of Medicine, Japan
  • Dr Yukio Sakiyama, Human Gene therapy, Hokkaido University Graduate School of Medicine, Japan
  • Dr Tetsuo Shirakawa, Center for Advanced Oral Medicine, Hokkaido University Hospital, Japan
  • Dr Yasutaka Yawaka, Department of Dentistry for Children and Disabled Person, Hokkaido University Graduate School of Dental Medicine, Japan
  • Dr Tadashi Ariga, Department of Pediatrics,Hokkaido University Graduate School of Medicine, Japan

    • Patients with disorders related to the teeth formation are occasionally encountered in the ordinary dental clinic. However, those with genetic disorders seem to be rare. We had a chance to examine 4 families with suspected hereditary dental disorders for 5 years. In this presentation, we will show their features and the results of molecular studies for them. Those features were characteristic and different each other. Target genes analyzed were amelogenin gene (AMELX), enamelin gene (ENAM), enamelysin gene (MMP-20), distal-less homeobox3 gene (DLX3), kallikrein-4 (KLK4) and dentin sialophosphoprotein gene (DSPP). We detected mutations in 3 of 4 families. First family members were suspected to have an autosomal dominant amelogenesis imperfecta (AI). One base deletion at exon 9–intron 9 junction of the ENAM, was detected. Second family members were considered as X-linked AI; the female proband and her sister showed mild phenotype compared with their father. We found a substitution of P52R in exon 5 of the AMELX; heterozygous in female patients and hemizygous in their father. Because the same substitution was not detected in the healthy family members or 100 healthy controls and this proline is highly conserved among other mammalians, we concluded that this is a mutation for the disease. The difference of phenotype between female and male patients in this family highly indicated their X-linked inheritance. Third family members showed dentinogenesis inperfecta (DGI) suspected as autosomal dominant inheritance. Affected individuals showed discoloration and severe attrition of their teeth. The missense mutation; V18D in exon 3 of the DSPP was detected. This substitution was not found in unaffected family members or control individuals. We could not identify the responsible gene for fourth family members with unclassified AI of unknown inheritance mode. Further study will be needed to identify novel responsible gene(s) for hereditary disorders of the teeth formation, and to establish the new classification of these disorders based on the molecular basis.

    Conference Organiser - ICMS Pty Ltd