Non-syndromic Oligodontia with a Novel Mutation of PAX9
Non-syndromic Oligodontia with a Novel Mutation of PAX9
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DOI：
10.1177/0022034510390042
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发表时间：
2011-03-01
影响因子：
7.6
通讯作者：
Moriyama, K.
中科院分区：
文献类型：
--
作者：
Suda, N.;Ogawa, T.;Moriyama, K.
恒牙发育不全是一种常见于人类的先天性畸形。少齿症是一种严重的牙齿发育类型，包括6颗或更多的先天性牙齿缺失，第三磨牙除外。先前的研究表明，同源框基因MSX1、配对结构域转录因子PAX9和EDA的突变与非综合征性少齿症有关。本研究报告了一个日本家庭（14个家庭成员中的8个）患有非综合征性少齿症，优先缺乏臼齿。在该家族中，在PAX9的配对结构域发现了一个新的移码突变（321_322insG）。移码突变导致配对结构域的氨基酸发生改变，导致26个氨基酸的翻译提前终止。转染COS-7细胞后，321_322insG PAX9的mRNA表达量与野生型PAX9相当。然而，321_322insG PAX9的mRNA比野生型PAX9更不稳定。通过Western blot分析和免疫染色评估，这种mRNA的不稳定性导致蛋白质产量显著下降。这些研究结果表明，321_322insG突变导致PAX9蛋白功能不足和单倍不全作为家族性PAX9突变的非综合征性少齿症的遗传模型。
Agenesis of the permanent teeth is a congenital anomaly that is frequently seen in humans. Oligodontia is a severe type of tooth agenesis involving 6 or more congenitally missing teeth, excluding the third molars. Previous studies have indicated that mutations in the homeobox gene MSX1, paired domain transcription factor PAX9, and EDA are associated with non-syndromic oligodontia. This study reports a Japanese family (eight of 14 family members affected) with non-syndromic oligodontia who preferentially lacked molar teeth. In this family, a novel frameshift mutation (321_322insG) was identified in the paired domain of PAX9. The frameshift mutation caused altered amino acids in the paired domain and premature termination of translation by 26 amino acids. When transfected into COS-7 cells, the mRNA expression of 321_322insG PAX9 was comparable with that of wild-type PAX9. However, the mRNA of 321_322insG PAX9 was more unstable than that of wild-type PAX9. This mRNA instability caused a marked decrease in protein production, as evaluated by Western blot analysis and immunostaining. These findings suggest that the 321_322insG mutation causes insufficient function of PAX9 protein and haploinsufficiency as a genetic model of familial non-syndromic oligodontia with a PAX9 mutation.