Phenotypes and genotypes in 2 DGI families with different DSPP mutations

Area of Science:

• Genetics
• Biochemistry
• Dental Science

Background:

• Dentinogenesis Imperfecta type II (DGI-II) is a genetic disorder affecting dentin formation.
• Mutations in the Dentin Sialophosphoprotein (DSPP) gene are implicated in DGI-II.
• Understanding genotype-phenotype correlations is crucial for diagnosis and management.

Purpose of the Study:

• To characterize dentin ultrastructure resulting from DSPP gene mutations.
• To define phenotypes associated with specific DSPP mutations in DGI-II families.

Main Methods:

• Phenotypic and genotypic analysis of two DGI-II families.
• DSPP exon amplification and sequencing for mutation identification.
• Scanning and transmission electron microscopy for dentin ultrastructure examination.

Main Results:

• Affected individuals exhibited teeth discoloration, attrition, and obliterated pulp chambers.
• A nonsense mutation (c.133CT) in DSPP was identified in family 1, associated with "shell" teeth.
• A missense mutation (c.52GT) in DSPP was identified in family 2.
• Ultrastructural analysis revealed irregular dentin tubules, abnormal enamel, and fibril bundles in family 1.

Conclusions:

• A nonsense mutation in DSPP causes characteristic tooth ultrastructural changes.
• DSPP mutations c.133CT and c.52GT may be mutation hotspots.
• Identical DSPP mutations can lead to diverse clinical phenotypes in unrelated DGI families.