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A novel splice acceptor mutation in the DSPP gene causing dentinogenesis imperfecta type II
1Department of Biological and Material Sciences, University of Michigan Dental Research Laboratory, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA.
Human Genetics
|July 9, 2004
Summary
A novel mutation in the dentin sialophosphoprotein (DSPP) gene causes autosomal dominant dentinogenesis imperfecta type II, a condition linked to progressive hearing loss. This discovery clarifies the genetic basis for certain inherited dentin defects.
Area of Science:
- Genetics
- Dentistry
- Otolaryngology
Background:
- The dentin sialophosphoprotein (DSPP) gene encodes key dentin matrix proteins, and its defects cause inherited dentin abnormalities.
- These dentin defects can be associated with progressive high-frequency sensorineural hearing loss.
- Clinical classifications include dentinogenesis imperfecta (DGI) types I, II, and III, and dentin dysplasia types I and II, with unknown genetic underpinnings for this heterogeneity.
Purpose of the Study:
- To investigate the genetic basis of inherited dentin defects and associated hearing loss in a kindred with autosomal dominant DGI type II.
- To identify the specific mutation responsible for the observed clinical phenotype.
Main Methods:
- Genetic analysis of an 11-member kindred affected with autosomal dominant DGI type II.
- Mutation screening of the DSPP gene, specifically focusing on intron regions.
- Correlation of identified mutations with clinical affection status and absence in unaffected individuals.
Main Results:
- A novel mutation (g.1188C-->G, IVS2-3C-->G) was identified in intron 2 of the DSPP gene in affected individuals.
- This mutation altered the intron sequence and was strongly correlated with the disease phenotype.
- The mutation was absent in 104 unaffected individuals from the same ethnic and geological background.
- Clinical features included primary dentition with pulp exposures, enamel abrasion, dentin wear, and progressive pulp obliteration; adult permanent dentition showed severe attrition, tooth loss, and reconstruction needs.
- Mild high-frequency hearing loss was observed in the oldest affected member.
Conclusions:
- The identified DSPP gene mutation is the likely cause of autosomal dominant DGI type II in this kindred.
- This finding elucidates the genetic etiology of a specific pattern of inherited dentin defects.
- The study highlights the pleiotropic effects of DSPP mutations, linking dentin abnormalities with sensorineural hearing loss.