Unique enamel phenotype associated with amelogenin gene (AMELX) codon 41 point mutation

Different mutations in the amelogenin gene (AMELX) result in the markedly d ifferent enamel phenotypes that are collectively known as amelogenesis impe rfecta (AI). We hypothesize that unique phenotypes result from specific gen etic mutations. The purpose of this study was to characterize the enamel co mpositional and structural features associated with a specific AMELX mutati on in three families with X-linked Al. We performed mutational analysis by amplifying AMELX exons and sequencing the products. Permanent and primary a ffected (N = 6) and normal (N = 3) teeth were collected and examined by lig ht, scanning, and transmission electron microscopy. Enamel proteins were ev aluated by immunolocalization of amelogenin and amino acid analysis. AI-aff ected individuals all shared a common AMELX point mutation (C to A change a t codon 41). The dental phenotypic findings were remarkably consistent in a ll affected individuals. The AI enamel was opaque, with numerous prism defe cts or holes encompassing the entire prism width. Affected crystallites app eared more radiolucent and morphologically less uniform, compared with that of normal enamel. Immunogold labeling with anti-amelogenin antibodies loca lized amelogenin to the crystallites but not to the inter-crystalline space s. No immunogold labeling was seen in normal enamel. There was an increased and amelogenin-like protein content in AI enamel (0.95%) compared with nor mal enamel (0.13%). We conclude that this codon 41 C to A missense point mu tation, in a highly conserved region of the AMELX gene, results in a remark ably consistent phenotype.