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

无釉发育不全（AI）是一组影响牙釉质形成的遗传性疾病，其特点是临床和遗传异质性。它在遗传上分为两种形式，由突变的淀粉原基因引起的x连锁和antosomal。迄今为止，除了编码釉素的基因突变导致的几种类型外，还没有发现任何一种常染色体AI的基因，尽管它们更为普遍。我们最近克隆了人类成釉蛋白基因。它是一个位于人类染色体4q21上的非釉素蛋白，作为一个单拷贝基因，与釉素基因紧密相连。因此，成釉酶基因也被认为是常染色体AI的候选基因，有必要了解AI与成釉酶基因之间的关系，并建立基因诊断标准。作为第一步，我们研究了未表现出AI迹象的亚洲受试者的成釉酶基因多态性，以便作为AI患者基因评估的比较点。采用聚合酶链反应和基因组DNA测序技术，对23名亚洲人（19名日本人、2名中国人、1名斯里兰卡人和1名泰国人）的成釉酶基因进行了筛选。结果，我们检测到6个同义取代，4个非同义取代和连续的3个核苷酸缺失，导致翻译区域氨基酸残基缺失。在3'非翻译区和内含子中也检测到其他的替换和缺失。我们的研究结果为评估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，尚未发现AI患者成釉细胞素和成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