The relationship between autosomal amelogenesis imperfecta and tooth-specific genes, and the gene diagnosis

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Amelogenesis imperfecta(AI) is a group of inherited disorders affecting enamel formation that are characterized by clinical and genetic heterogeneity. It is genetically classified into two forms, X-linked caused by the mutated amelogenin gene and autosomal. To date, only several types resulted from mutations of the gene encoding enamelin, kalliklein 4, enamelysin, and DLX3 although they are much more prevalent than X-linked form. We have recently cloned the human ameloblastin gene. Ameloblastin is one of the extracellular matrix proteins in tooth enamel and may be responsible for autosomal amelogenesis imperfecta(AI), since it plays a significant role in enamel crystal growth. Hence, the ameloblastin gene is also considered to be a candidate responsible for autosomal AI. We investigated polymorphisms of the human ameloblastin gene by polymerase chain reaction, DNA sequencing and single-strand conformational polymorphism(SSCP) analysis using genomic DNA from 50 Japanese subjects with sound dentition. One single sequential trinucleotide deletion and 3 single-nucleotide polymorphisms(SNPs) were identified in the translated region. The nucleotide deletion results in the lack of an amino acid residue and 2 of the SNPs cause nonsynonymous substitutions of amino acid residues. These results provide important background information for the investigation of autosomal AI in Japanese patients. Subsequently, we focussed our attention on the ameloblastin genes of 3 Japanese patients and also investigated the gene encoding enamelin and enamelysin. However, no pathogenic mutation in these genes of AI patients was detected. It was suggested that the exploration was extended to promoter regions of them, as well as coding regions of other expectant genes.