Molecular Characterization of Amelogenesis Imperfecta in Chinese Patients
Molecular Characterization of Amelogenesis Imperfecta in Chinese Patients
复制标题
中国患者牙釉质生成不全的分子特征
DOI：
10.1159/000334210
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Bian, Z.
中科院分区：
文献类型：
--
作者：
Song, Y. L.;Wang, C. N.;Bian, Z.
背景：6个基因的突变已被确定为在分离条件下具有各种表型的无染色体发育不全（AI）的病因的一部分。其中FAM83H基因是导致功能未知AI病因的主要因素。目的：本研究旨在了解中国AI患者的表型和分子特征，分析FAM83H蛋白的结构和功能。方法：从中国人群中选取6个低钙化AI家族和3个发育不良AI家族。通过扩增和测序FAM83H和ENAM基因的所有外显子（包括内含子-外显子边界）进行突变分析。采用生物信息学方法对FAM83H蛋白进行了结构建模和功能分析。结果：所有患者均未见明显的前牙开咬。在6个低钙化AI家族中，5个家族在FAM83H基因c端分别发现了5个突变（c.906T>G、c.924dupT、c.973C>T、c.1354C>T和c.2029C>T），在3个发育不良AI家族中，1个家族在ENAM基因中发现了c.534 + 1G> a剪接突变。通过同源性建模生成FAM83H的N端和c端结构模型。FAM83H n端预测结构与具有GT-A折叠的糖基转移酶结构相似，FAM83H c端预测结构与I型胶原蛋白结构相似。结论：据我们所知，这是中国血统家庭中具有特定分子变异的AI的第一份报告。我们的研究为FAM83H蛋白的结构和功能提供了新的见解。
Background: Mutations in 6 genes have been identified as being part of the etiology of amelogenesis imperfecta (AI) with various phenotypes in an isolated condition. Among them the FAM83H gene is the major contributor to the etiology of AI with unknown function. Objective: This study aims to determine the phenotypic and molecular characterization of Chinese AI patients and to analyze the structure and function of the FAM83H protein. Methods: We enrolled 6 hypocalcified AI and 3 hypoplastic AI families from the Chinese population. Mutation analysis was performed by amplifying and sequencing all exons including intron-exon borders for FAM83H and ENAM genes. Structural modeling and function analysis on the FAM83H protein were carried out by bioinformatic processing. Results: No obvious anterior open bite was observed in all the investigated individuals. Five mutations (c.906T>G, c.924dupT, c.973C>T, c.1354C>T and c.2029C>T) in the C-terminal of the FAM83H gene were revealed, respectively, in 5 out of 6 hypocalcified AI families, and a splicing mutation c.534 + 1G>A in the ENAM gene was identified in 1 out of 3 hypoplastic AI families. Structural models of the N- and C-terminal regions of FAM83H were generated by homology modeling. The predicted structure of the FAM83H N-terminal shows resemblance to that of glycosyltransferases with GT-A folds, and the predicted structure of the FAM83H C-terminal possesses similarity to type I collagen protein. Conclusions: To our knowledge, this is the first report of AI with specific molecular variations in families of Chinese descent. Our study provides new insights into the structure and function of the FAM83H protein.