The relationship between amelogenesis imperfecta and ameloblastin/amelogenin genes, and the gene diagnosis

牙釉质发育异常（AI）是一组影响釉质形成的遗传性疾病，具有临床和遗传异质性。遗传学上分为两种类型，X连锁型和自体染色体型。到目前为止，除了少数几种由编码釉蛋白的基因突变引起的类型外，还没有发现常染色体AI的潜在基因，尽管它们更为普遍。我们最近克隆了人成釉蛋白基因。它是位于人类染色体4q21上作为单拷贝基因的非釉原蛋白，并且与釉蛋白基因紧密连锁。因此，成釉蛋白基因也被认为是常染色体AI的候选基因，了解AI与成釉蛋白基因之间的关系，建立基因诊断标准是必要的。作为第一步，我们调查成釉蛋白基因的多态性在亚洲人谁没有表现出AI的迹象，以便作为比较点，在AI患者的基因评估。采用聚合酶链反应和DNA测序技术对23例亚洲受试者（19例日本人，2例中国人，1例斯里兰卡人和1例泰国人）的成釉蛋白基因进行了筛选。结果发现，在该基因的翻译区有6个同义替换，4个非同义替换和3个连续的核苷酸缺失，导致一个氨基酸残基的缺失。在3 '非翻译区和内含子中也发现了其它的替换和缺失。本研究结果为评价成釉蛋白基因是否与亚洲人群常染色体AI相关提供了有用的信息。然而，尚未检测到AI患者的成釉蛋白和釉原蛋白基因的致病性突变

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