Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II
Clinical, histopathologic, and genetic investigation in two large families with dentinogenesis imperfecta type II
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DOI：
10.1007/s00439-004-1084-z
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发表时间：
2004-04-01
期刊：
影响因子：
5.3
通讯作者：
Norgren, S
中科院分区：
文献类型：
--
作者：
Malmgren, B;Lindskog, S;Norgren, S
Dentinogenesis proximata（DI）II型是一种影响牙本质的遗传性疾病，与染色体4 q21上的牙本质唾液磷蛋白（DSPP）基因突变有关。基因产物被切割成两种牙本质特异性基质蛋白，牙本质唾液蛋白（DSP）和牙本质磷蛋白。本调查的目的是研究基因型和表型在两个受影响的家庭，特别是参考临床，影像学和组织病理学表现。家庭A和家庭B的五个受影响的成员进行了临床和放射学记录，分别有14和10颗牙齿，可用于组织病理学调查和准备地面部分，这是半定量评估的牙本质发育不良的表现，根据评分系统，发育不良的牙本质评分（DDS）。从A家族的6名受累成员和10名未受累成员以及B家族的8名受累成员和6名未受累成员中采集静脉血样。提取基因组DNA并用于序列分析。这两个家族呈现不同的错义突变。在A家族所有6个分析的受影响个体中，均发现DSP基因部分的Arg 68 Trp错义突变。这种突变在10名健康成员中均不存在。在家庭B，一个Ala 15 Val错义突变，涉及最后一个残基的信号肽被发现在所有8个受影响的，但没有在6个健康的成员。B家族的临床和影像学障碍及DDS更严重。这些数据表明在II型DI中存在基因型-表型相关性。
Dentinogenesis imperfecta (DI) type II, an inherited disorder affecting dentin, has been linked to mutations in the dentin sialophosphoprotein (DSPP) gene on chromosome 4q21. The gene product is cleaved into two dentin-specific matrix proteins, dentin sialoprotein (DSP) and dentin phosphoprotein. The aim of this investigation was to study genotypes and phenotypes in two affected families with special reference to clinical, radiographic, and histopathologic manifestations. Seven affected members of Family A and five of Family B were documented clinically and radiographically; 14 and 10 teeth, respectively, were available for histopathologic investigation and prepared for ground sections, which were assessed semiquantitatively for dysplastic manifestations in the dentin according to the scoring system, dysplastic dentin score (DDS). Venous blood samples were collected from six affected and ten unaffected members of Family A, and from eight affected and six unaffected members of Family B. Genomic DNA was extracted and used for sequence analyses. The two families presented with different missense mutations. An Arg68Trp missense mutation in the DSP part of the gene was revealed in all six analyzed affected individuals in Family A. This mutation was not present in any of the ten healthy members. In Family B, an Ala15Val missense mutation involving the last residue of the signal peptide was found in all eight affected but in none of the six healthy members. The clinical and radiographic disturbances and DDS were more severe in Family B. The data indicate the presence of a genotype-phenotype correlation in DI type II.