The relationship between autosomal amelogenesis imperfecta and tooth-specific 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。遗传上分为两种类型，X连锁型和常染色体型。迄今为止，只有几种类型是由编码釉蛋白、激肽4、溶釉蛋白和DLX3的基因突变引起的，尽管它们比X连锁形式普遍得多。我们最近克隆了人成釉蛋白基因。成釉蛋白是牙釉质中的细胞外基质蛋白之一，由于其在釉质晶体生长中起重要作用，因此可能与常染色体釉质形成相关。因此，成釉蛋白基因也被认为是负责常染色体AI的候选基因。我们采用聚合酶链反应、DNA测序和单链构象多态性（SSCP）分析方法，对50名日本健康牙列受试者的基因组DNA进行了人成釉蛋白基因多态性研究。在翻译区发现了一个单一的连续三核苷酸缺失和3个单核苷酸多态性（SNP）。核苷酸缺失导致氨基酸残基的缺失，2个SNP导致氨基酸残基的非同义取代。这些结果提供了重要的背景资料，为调查日本患者的常染色体AI。随后，我们将注意力集中在3例日本患者的成釉蛋白基因上，并研究了编码釉蛋白和溶釉蛋白的基因。然而，在AI患者的这些基因中未检测到致病性突变。这表明，探索扩展到启动子区，以及其他的预期基因的编码区。

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.