Mutational analysis of candidate genes in 24 amelogenesis imperfecta families
Mutational analysis of candidate genes in 24 amelogenesis imperfecta families
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DOI：
10.1111/j.1600-0722.2006.00278.x
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发表时间：
2006-05-01
影响因子：
1.9
通讯作者：
Hu, Jan C. -C.
中科院分区：
文献类型：
--
作者：
Kim, Jung-Wook;Simmer, James P.;Hu, Jan C. -C.
釉质发生不全是一组牙釉质形成过程中的异质性遗传性缺陷。畸形的牙釉质可能异常稀薄、柔软、粗糙和有色。人工智能的严格定义只包括那些在没有其他症状的情况下出现釉质缺陷的病例。目前，有7个AI候选基因：釉原蛋白、釉蛋白、成釉蛋白、Tuftelin、远端无同源盒3、釉解素和激肽释放酶4。为了确定孤立的釉质缺陷患者AI候选基因的序列变异，并推断每个序列变异对蛋白表达和结构的可能影响，我们收集了孤立的釉质缺陷家系。以先证者基因组DNA为模板，扩增出每个AI候选基因的编码外显子和邻近内含子序列。对先证者的扩增产物进行测序。然后，对其他家庭成员进行测试，以确定他们针对每个序列变异的基因型。所有受试者都接受了口腔检查，并获得了口腔内照片和牙科X光片。在24个孤立的釉质缺陷家系中，只在AI候选基因中发现了6个致病突变。这一发现表明，许多额外的基因可能与AI的病因学有关。
Amelogenesis imperfecta (AI) is a heterogeneous group of inherited defects in dental enamel formation. The malformed enamel can be unusually thin, soft, rough and stained. The strict definition of AI includes only those cases where enamel defects occur in the absence of other symptoms. Currently, there are seven candidate genes for AI: amelogenin, enamelin, ameloblastin, tuftelin, distal-less homeobox 3, enamelysin, and kallikrein 4. To identify sequence variations in AI candidate genes in patients with isolated enamel defects, and to deduce the likely effect of each sequence variation on protein expression and structure, families with isolated enamel defects were recruited. The coding exons and nearby intron sequences were amplified for each of the AI candidate genes by using genomic DNA from the proband as template. The amplification products for the proband were sequenced. Then, other family members were tested to determine their genotype with respect to each sequence variation. All subjects received an oral examination, and intraoral photographs and dental radiographs were obtained. Out of 24 families with isolated enamel defects, only six disease-causing mutations were identified in the AI candidate genes. This finding suggests that many additional genes potentially contribute to the etiology of AI.