AMELX Deletion and p.P70T Mutation Display Different Enamel Phenotypes

Amelogenin is critical for proper dental enamel formation. Fifteen AMELX defects associated with amelogenesis imperfecta (AI) have been reported and used to ascertain genotype-phenotype correlations. Such analyses attempt to distinguish phenotypes caused by haploinsufficiency, partial loss of function, and secondary pathology. Objective: To identify AMELX defects in kindreds with X-linked AI. Methods: All AMELX coding exons and adjoining intron sequences were amplified by polymerase chain reaction (PCR) and characterized by DNA sequencing. Enamel phenotypes were characterized by intraoral examinations, oral photographs and radiographs. Results: AMELX defects were characterized in two un-related AI kindreds. The first was a partial deletion in ARHGAP6 that completely deleted AMELX. None of the seven AMELX exons could be amplified from the proband, although upstream and downstream PCR products in ARHGAP6 were detected. The male proband showed a thin layer of rough, yellow-colored mineral covering the crowns that contrasted with dentin on radiographs. The enamel was whiter and thicker at the incisal edges and cusp tips. The affected mother showed thin enamel with vertical white bands resembling dental fluorosis. The second AMELX defect was a previously characterized C to A transversion (c.208C>A) that replaced proline at position 70 with threonine (p.P70T). The female proband's dentition exhibited mild taurodontism and displayed areas of rough, brown-hypoplastic and nearly-normal enamel that did not alternate in vertical banding patterns. Conclusion: We have characterized two kindreds with X-linked AI, which provides new information relevent to AMELX genetype-phenotype correlations. This study was supported by NIDCR grant DE015846.