A novel splice site mutation in the dentin sialophosphoprotein gene in a Chinese family with dentinogenesis imperfecta type II
A novel splice site mutation in the dentin sialophosphoprotein gene in a Chinese family with dentinogenesis imperfecta type II
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DOI：
10.1016/j.mrfmmm.2008.11.019
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发表时间：
2009-03-09
影响因子：
2.3
通讯作者：
Li, XiaoJun
中科院分区：
文献类型：
--
作者：
Wang, HaoYang;Hou, YanNing;Li, XiaoJun
研究了一个中国家族中的24个个体，这些个体跨越了6代人，这些个体患有明显的常染色体显性形式的牙本质发生型II型（DGI-II，OMIM #125490）。所有受影响的个人提出了典型的，临床和影像学特征的DGI-II，但没有双边进行性高频感音神经性听力损失。为了研究突变的分子，使用位置候选方法来确定该家族中的突变基因。基因组DNA从24个受影响的个人，18个未受影响的亲属的家庭和50个对照。使用白细胞DNA对4号染色体上存在的6个短串联重复序列（STR）标记（D4 S1534、GATA 62 A11、DSPP、DMP 1、SPP 1和D4 S1563）进行单倍型分析。在D4 S1534和DMP 1之间的关键区域，牙本质涎磷蛋白（DSPP）基因（OMIM *125485）被认为是最强的候选基因。使用来自同一家族的24个受影响个体和18个未受影响亲属的DNA分析该基因的前四个外显子和外显子/内含子边界。DNA测序显示内含子2中的杂合缺失突变（在位置-3至-25处），其导致移码突变，将受体位点序列从CAG改变为AAG（IVS 2 -3C -> A），并且还可能破坏内含子2中的分支点共有序列。在24名受影响的个体中发现了这种突变，但在18名未受影响的亲属和50名对照中没有发现。通过等位基因特异性测序和变性高效液相色谱（DHPLC）分析鉴定缺失。我们的结论是杂合缺失突变的发病机制的DGI-II。(C)2008 Elsevier B. V.保留所有权利。
Twenty-four individuals were investigated that spanned six generations in a Chinese family affected with an apparently autosomal dominant form of dentinogenesis imperfecta type II (DGI-II, OMIM #125490). All affected individuals presented with typical, clinical and radiographic features of DGI-II, but without bilateral progressive high-frequency sensorineural hearing loss. To investigate the mutated molecule, a positional candidate approach was used to determine the mutated gene in this family. Genomic DNA was obtained from 24 affected individuals, 18 unaffected relatives of the family and 50 controls. Haplotype analysis was performed using leukocyte DNA for 6 short tandem repeat (STR) markers present in chromosome 4 (D4S1534, GATA62A11, DSPP, DMP1, SPP1 and D4S1563). In the critical region between D4S1534 and DMP1, the dentin sialophosphoprotein (DSPP) gene (OMIM *125485) was considered as the strongest candidate gene. The first four exons and exon/intron boundaries of the gene were analyzed using DNA from 24 affected individuals and 18 unaffected relatives of the same family. DNA sequencing revealed a heterozygous deletion mutation in intron 2 (at positions -3 to -25), which resulted in a frameshift mutation, that changed the acceptor site sequence from CAG to AAG (IVS2-3C -> A) and may also have disrupted the branch point consensus sequence in intron 2. The mutation was found in the 24 affected individuals, but not in the 18 unaffected relatives and 50 controls. The deletion was identified by allele-specific sequencing and denaturing high-performance liquid chromatography (DHPLC) analysis. We conclude that the heterozygous deletion mutation contributed to the pathogenesis of DGI-II. (C) 2008 Elsevier B.V. All rights reserved.