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

釉质形成不全与成釉细胞/釉原蛋白基因的关系及基因诊断

基本信息

批准号：
13672147
负责人：
SHINTANI Seikou
金额：
$ 0.64万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672147/
关键词：
ameJogenesisimperfecta ameloblastin amelogenin gene polymorphism Asian アジア人遺伝性疾患

项目摘要

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

釉质发生不全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的特点。它在遗传学上分为两种形式，一种是由釉原蛋白基因突变引起的X连锁，另一种是反染色体。到目前为止，除了编码釉质蛋白的基因突变引起的少数几种类型外，还没有鉴定出常染色体AI的潜在基因，尽管它们要普遍得多。我们最近克隆了人成釉蛋白基因。它是一种非釉原蛋白，位于人类染色体4q21上，为单拷贝基因，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，有必要了解AI与成釉蛋白基因的关系，并建立基因诊断的标准。作为第一步，我们调查了成釉蛋白基因在没有AI迹象的亚洲受试者中的多态性，以便作为评估AI患者基因的比较点。应用聚合酶链式反应和DNA测序技术对23例亚洲受试者(日本19例，中国2例，斯里兰卡1例，泰国1例)的成釉蛋白基因进行了筛查。作为结果，我们检测到6个同义替换，4个非同义替换和3个核苷酸顺序缺失导致翻译区域的一个氨基酸残基缺失。在3‘非翻译区和内含子中也检测到了其他的替换和缺失。我们的发现为评估成釉蛋白基因是否与亚洲人群常染色体AI有关提供了有用的信息。然而，尚未检测到AI患者成釉蛋白和成釉蛋白基因的致病突变。