The Enamelin Gene Mutation in an Autosomal Dominant Amelogenesis Imperfecta

Objectives: Amelogenesis imperfecta (AI) is a genetic disorder affecting the enamel of both deciduous and permanent teeth. In this study, we investigated the ameloblastin and enamelin genes in a Japanese family with a possible autosomal-dominant form of AI. Previous studies have mapped an autosomal-dominant human AI locus to chromosome 4q11-q21, where two candidate genes, ameloblastin and enamelin, are located.

Methods: The affected individuals were the father and his second son who had teeth with thin, smooth, yellowish enamel. The mother and her eldest son did not show abnormalities in their tooth enamel. After informed consent, genomic DNA was isolated from peripheral-blood mononuclear cells of the affected and unaffected individuals in the family. We performed a mutation analysis of the ameloblastin and enamelin genes using PCR. The PCR amplified fragments were directly sequenced using ABI-PRISM Big Dye and the 373A sequencer. This study was conducted with the approval of the Ethical Committee of Tokyo Dental College.

Results: Sequencing of the DNA fragment revealed a deletion of a single-G from a series of 7 G residues (AGGGGGGGTAAGT->AGGGGGGTAAGT) at the exon 9-intron 9 boundary of the enamelin gene. This mutation was confirmed in all affected individuals but was not found in unaffected family members. There was no mutation in the ameloblastin gene in this family. Conclusion: The effect of this deletion is suggested to result in an alteration of the reading frame from exon 9, and the introduction of a premature stop codon at 277 in exon 10. Heterogeneous mutations in the enamelin gene are responsible for an autosomal-dominant hypoplastic form of AI.