Frameshift mutations in dentin phosphoprotein and dependence of dentin disease phenotype on mutation location.

[dentinogenesis imperfecta]

We describe results from a mutational analysis of the region of the dentin sialophosphoprotein (DSPP ) gene encoding dentin phosphoprotein (DPP ) in 12 families with dominantly inherited dentin diseases . In eight families (five mutations in the N-terminal third of DPP ), the clinical and radiologic features were uniform and compatible with dentin dysplasia type II (DD-II ) with major clinical signs in the deciduous dentition . In the other families (four mutations in the more C-terminal part ), the permanent teeth also were affected , and the diseases could be classified as variants of dentinogenesis imperfecta . Attrition was not prominent , but periapical infections were common . Discoloring with varying intensity was evident , and pulps and root canals were obliterated in the permanent dentition . All mutations caused a frameshift that replaced the Ser-Ser-Asx repeat by a code for a hydrophobic downstream sequence of approximately original length . We conclude that frameshift mutations in DSPP explain a significant part of dentin diseases . Furthermore , we propose that the location of the mutation is reflected in the phenotypic features as a gradient from DD-II to more severe disease that does not conform to the classic definitions of DI -II .

Diseases
Validation

Diseases presenting "severe disease" symptom

allergic bronchopulmonary aspergillosis

alpha-thalassemia

dentin dysplasia

dentinogenesis imperfecta

dystrophic epidermolysis bullosa

familial hypocalciuric hypercalcemia

familial mediterranean fever

krabbe disease

lymphangioleiomyomatosis

neonatal adrenoleukodystrophy

pyomyositis

severe combined immunodeficiency

systemic capillary leak syndrome

wolf-hirschhorn syndrome

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