A novel nonsense mutation in PAX9 is associated with sporadic hypodontia.
A novel nonsense mutation in PAX9 is associated with sporadic hypodontia.
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DOI：
10.1093/mutage/ger080
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发表时间：
2012-05
期刊：
影响因子：
2.7
通讯作者：
Junxia Zhu;Xiang Yang;Chenying Zhang;L. Ge;Shuguo Zheng
中科院分区：
文献类型：
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作者：
Junxia Zhu;Xiang Yang;Chenying Zhang;L. Ge;Shuguo Zheng
在牙齿发育的调控过程中，最重要的事件是上皮和间充质组织之间的诱导相互作用。Pax9的表达已被证明在任何形态学表现之前特异性地标记所有牙齿的预期部位处的间充质区域。在这里，我们调查了PAX9基因作为一个候选基因的缺牙在5个无关的中国患者的牙齿发育不全。直接测序和限制性内切酶分析发现一个新的杂合突变c.480C>G（p.160Tyr>X，Y160X）在一个病人谁失去了20个恒牙（第三磨牙除外）和6个乳牙。该突变为无义突变，导致PAX9基因外显子2提前终止密码子。从受影响的个人培养的淋巴细胞的互补DNA的PCR分析不能表明突变的转录的完全降解。启动子报告基因检测显示突变的PAX9蛋白的转录活性降低，表明严重的表型可能是由PAX9的单倍不足引起的。在另一个有15颗恒牙缺失（第三磨牙除外）的患者中，我们发现了斯托克顿先前报道的c.219insG突变。
The most important events during the regulation of tooth development were inductive interactions between the epithelial and mesenchymal tissues. The expression of Pax9 had been shown to specifically mark the mesenchymal regions at the prospective sites of all teeth prior to any morphological manifestations. Here, we investigated the PAX9 gene as a candidate gene for hypodontia in five unrelated Chinese patients with tooth agenesis. Direct sequencing and restriction enzyme analysis revealed a novel heterozygous mutation c.480C>G (p.160Tyr>X, Y160X) in a patient who was missing 20 permanent teeth (the third molars excluded) and 6 primary teeth. The mutation was a nonsense mutation, leading to a premature stop codon in exon 2 of PAX9 gene. PCR analysis of complementary DNA from cultured lymphocytes of the affected individual could not indicate the complete degradation of the mutated transcript. Promoter reporter assays revealed reduced transcriptional activity of the mutated PAX9 protein suggesting that the severe phenotype may result from haploinsufficiency of PAX9. In another patient with 15 missing permanent teeth (the third molars excluded), we found the c.219insG mutation previously reported by Stockton.