The relationship between amelogenesis imperfecta and ameloblastin/amelogenin 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 antosomal. To date, none of the gene underlying autosomal AI has been identified except only a few types resulted from mutations of the gene encoding enamelin although they are much more prevalent. We have recently cloned the human ameloblastin gene. It is a nonamelogenin protein located on human chromosome 4q21 as a single copy gene and closely linked to the enamelin gene. Hence, the ameloblastin gene is also considered to be a candidate responsible for autosomal AI, and it is necessary to know the relationship between AI and ameloblastin genes and to establish the criteria for the gene diagnosis. As the first step, we investigate the polymorphisms of the ameloblastin gene hi Asian subjects who do not show signs of AI in order to use as comparative points in the evaluation on the genes of AI patients. The ameloblastin genes of 23 Asian subjects (19 Japanese, 2 Chinese, 1 Sri Lankan and 1 Thai) were screened by polymerase chain reaction and DNA sequencing using genomic DNA. As the results, we detected six synonymous substitutions, four nonsynonymous substitutions and sequential three nucleotides deletions causing the missing of an amino acid residue in the translated region. Other substitutions and deletions were also detected in the 3'untranslated region and introns. Our findings provide useful information for evaluating if the ameloblastin gene is related to autosomal AI in Asian population. However, no pathogenic mutation in the ameloblastin and amelogenin genes of AI patients has not been detected yet