PAX9 和 MSX1 转录因子基因与非综合征性牙齿缺失。

PAX9 and MSX1 transcription factor genes in non-syndromic dental agenesis.

机构信息

Departamento de Genética, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Caixa Postal 15053, 91501-970 Porto Alegre, RS, Brazil.

出版信息

Arch Oral Biol. 2011 Apr;56(4):337-44. doi: 10.1016/j.archoralbio.2010.10.020. Epub 2010 Dec 15.

DOI:10.1016/j.archoralbio.2010.10.020

PMID:21111400

Abstract

OBJECTIVE: The molecular variation of paired domain box gene 9 (PAX9) was previously investigated by our research group and a high degree of evolutionary conservation in coding and non-coding regions was observed except in exon 3. PAX9 is a transcription factor important in tooth development, and we wanted to verify its role in dental agenesis in detail. Since dental development is a complex trait we also decided to examine the influence of another transcription factor, muscle segment homeodomain-homeobox 1 (MSX1) on it. DESIGN: A total of 360 consecutively ascertained patients seeking orthodontic treatment were screened for tooth agenesis and 33% of them were found to have it. Thirty-five of those with agenesis and 15 controls had their DNA studied for PAX9 exons 2, 3, 4 and adjacent regions (total of 1476 base pairs, bp) as well as MSX1 exon 2 (698bp). A trio (a proband and her parents) was also studied. RESULTS: Six polymorphic sites were found, three in PAX9 exon 3 and three in MSX1 exon2. MSX1 rs1095 derived allele occurred in individuals with agenesis only, and two other mutations in this gene had been earlier associated with tooth agenesis. Homozygosity for the PAX9 Ala240Pro mutation was studied in a family (proband and her parents), suggesting recessive inheritance with variable expressivity for the dental agenesis found. CONCLUSION: Common variants located out of the DNA binding domain of the two PAX9 and MSX1 genes can also be related to tooth agenesis.

摘要

目的：我们的研究小组之前研究了配对域盒基因 9（PAX9）的分子变异，除了外显子 3 之外，在编码和非编码区域都观察到高度的进化保守性。PAX9 是牙齿发育中重要的转录因子，我们希望详细验证其在牙齿缺失中的作用。由于牙齿发育是一种复杂的特征，我们还决定研究另一个转录因子肌肉节同源框同源盒 1（MSX1）对其的影响。

设计：我们总共筛选了 360 名连续确定的寻求正畸治疗的患者，以筛查牙齿缺失症，其中 33%的患者患有牙齿缺失症。其中 35 名缺失症患者和 15 名对照者对 PAX9 外显子 2、3、4 及其相邻区域（总共 1476 个碱基对，bp）以及 MSX1 外显子 2（698bp）进行了 DNA 研究。还对一个三（先证者及其父母）进行了研究。

结果：发现了六个多态性位点，三个在外显子 3 中，三个在 MSX1 外显子 2 中。仅在外显子缺失症患者中发现了 MSX1 rs1095 衍生等位基因，而该基因中的另外两种突变先前与牙齿缺失症有关。在一个家庭（先证者及其父母）中研究了 PAX9 Ala240Pro 突变的纯合性，提示该牙齿缺失症具有可变外显率的隐性遗传。

结论：位于两个 PAX9 和 MSX1 基因 DNA 结合域之外的常见变体也可能与牙齿缺失症有关。