A novel missense mutation (p.P52R) in amelogenin gene causing X-linked amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a hereditary disease with abnormal dental enamel formation. Here we report a Japanese family with X-linked AI transmitted over at least four generations. Mutation analysis revealed a novel mutation (p.P52R) in exon 5 of the amelogenin gene. The mutation was detected as heterozygous in affected females and as hemizygous in their affected father. The affected sisters exhibited vertical ridges on the enamel surfaces, whereas the affected father had thin, smooth, yellowish enamel with distinct widening of inter-dental spaces. To study the pathological cause underlying the disease in this family, we synthesized the mutant amelogenin p.P52R protein and evaluated it in vitro. Furthermore, we studied differences in the chemical composition between normal and affected teeth by x-ray diffraction analysis and x-ray fluorescence analysis. We believe that these results will greatly aid our understanding of the pathogenesis of X-linked AI.