A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect.
A DSPP mutation causing dentinogenesis imperfecta and characterization of the mutational effect.
复制标题
DOI：
10.1155/2013/948181
复制
发表时间：
2013
影响因子：
--
通讯作者：
Kim JW
中科院分区：
文献类型：
--
作者：
Lee SK;Lee KE;Song SJ;Hyun HK;Lee SH;Kim JW
在非综合征遗传性牙本质缺陷中已发现DSPP基因突变，但基因型-表型相关性尚不完全清楚。最近有研究表明，影响IPV先导序列的DSPP突变导致突变的DSPP滞留在粗内质网（ER）中。在这项研究中，我们发现了一个患有牙本质发育不全III型的韩国家庭。为了确定该家族的致病突变，我们基于候选基因测序进行了突变分析。对DSPP基因的外显子和外显子-内含子边界进行了测序，并研究了所鉴定的突变对前mrna剪接和蛋白质分泌的影响。候选基因测序显示DSPP基因外显子2突变（c.50C > T, p.P17L）。剪接实验表明，突变不影响pre-mRNA剪接。然而，突变干扰了蛋白质分泌，导致突变蛋白大部分留在内质网。这些结果表明，该突变影响ER到高尔基体的输出，导致分泌的DSPP减少和ER过载。这可能导致细胞应激和损伤处理和/或运输牙本质基质蛋白或其他关键蛋白。
Mutations in the DSPP gene have been identified in nonsyndromic hereditary dentin defects, but the genotype-phenotype correlations are not fully understood. Recently, it has been demonstrated that the mutations of DSPP affecting the IPV leader sequence result in mutant DSPP retention in rough endoplasmic reticulum (ER). In this study, we identified a Korean family with dentinogenesis imperfecta type III. To identify the disease causing mutation in this family, we performed mutational analysis based on candidate gene sequencing. Exons and exon-intron boundaries of DSPP gene were sequenced, and the effects of the identified mutation on the pre-mRNA splicing and protein secretion were investigated. Candidate gene sequencing revealed a mutation (c.50C > T, p.P17L) in exon 2 of the DSPP gene. The splicing assay showed that the mutation did not influence pre-mRNA splicing. However, the mutation interfered with protein secretion and resulted in the mutant protein remaining largely in the ER. These results suggest that the mutation affects ER-to-Golgi apparatus export and results in the reduction of secreted DSPP and ER overload. This may induce cell stress and damage processing and/or transport of dentin matrix proteins or other critical proteins.
登录
查看更多内容
一种新型的DSPP突变与中国家族中II型牙毒发生Imperfecta有关。
影响因子：
--
作者：
Zhang, Xianqin;Chen, Lanying;Liu, Jingyu;Zhao, Zhen;Qu, Erjun;Wang, Xiaotao;Chang, Wei;Xu, Chengqi;Wang, Qing K.;Liu, Mugen
通讯作者：
Liu, Mugen
DOI：
10.1016/j.mrfmmm.2008.11.019
发表时间：
2009-03-09
影响因子：
2.3
作者：
Wang, HaoYang;Hou, YanNing;Li, XiaoJun
通讯作者：
Li, XiaoJun
影响因子：
30.8
作者：
Xiao, SX;Yu, C;Kong, XY
通讯作者：
Kong, XY
影响因子：
30.8
作者：
Zhang, XH;Zhao, J;Shen, Y
通讯作者：
Shen, Y
影响因子：
--
作者：
Bai H;Agula H;Wu Q;Zhou W;Sun Y;Qi Y;Latu S;Chen Y;Mutu J;Qiu C
通讯作者：
Qiu C