Novel dentin sialophosphoprotein gene frameshift mutations affect dentin mineralization

Area of Science:

• Genetics
• Dentistry
• Molecular Biology

Background:

• Inherited dentin defects are a group of genetic disorders affecting tooth structure.
• The dentin sialophosphoprotein (DSPP) gene is crucial for dentin formation and mineralization.
• Understanding the genetic basis of these defects is essential for diagnosis and potential therapies.

Purpose of the Study:

• To identify candidate genes responsible for inheritable dentin defects in three Chinese families.
• To characterize the physical and microstructural properties of teeth affected by these defects.
• To elucidate the impact of identified mutations on dentin formation and mineralization.

Main Methods:

• Clinical and radiological assessments of affected individuals.
• Whole-exome sequencing of genomic DNA from affected family members.
• In vitro analysis of dentin density, microhardness, and microstructure using SEM.

Main Results:

• Affected teeth exhibited abnormal yellowish-brown or milky coloration, obliterated pulp cavities, and sometimes shortened roots.
• Three novel frameshift mutations (c.2833delA, c.2852delG, c.3239delA) were identified in the DSPP gene.
• Mutations led to decreased dentin density and microhardness, sparse/disordered dentinal tubules, and abnormal dentinal-enamel junction (DEJ).

Conclusions:

• Three novel DSPP gene mutations are associated with inheritable dentin defects.
• These mutations likely cause abnormal dentin phosphoprotein (DPP) coding, impairing dentin mineralization.
• The findings expand the known spectrum of DSPP mutations and enhance understanding of dentinogenesis.