Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function, Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
J Dent Res. 2011 Mar;90(3):382-6. doi: 10.1177/0022034510390042. Epub 2010 Nov 22.
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.
恒牙缺失是一种常见的人类先天性异常。少牙症是一种严重的牙齿缺失症，涉及 6 颗或更多先天性缺失的牙齿，不包括第三磨牙。先前的研究表明，同源盒基因 MSX1、配对域转录因子 PAX9 和 EDA 的突变与非综合征性少牙症有关。本研究报道了一个日本家族（14 名家族成员中有 8 人受影响）患有非综合征性少牙症，该家族优先缺乏磨牙。在这个家族中，在 PAX9 的配对域中发现了一个新的移码突变（321_322insG）。移码突变导致配对域中的氨基酸改变，并通过 26 个氨基酸提前终止翻译。当转染到 COS-7 细胞中时，321_322insG PAX9 的 mRNA 表达与野生型 PAX9 相当。然而，与野生型 PAX9 相比，321_322insG PAX9 的 mRNA 更不稳定。这种 mRNA 不稳定性导致蛋白产量明显下降，如通过 Western blot 分析和免疫染色评估。这些发现表明，321_322insG 突变导致 PAX9 蛋白功能不足和单倍不足，作为具有 PAX9 突变的家族性非综合征性少牙症的遗传模型。
