Institute of Biotechnology, Biological Sciences Center, University of Caxias do Sul, Caxias do Sul, Brazil.
J Oral Pathol Med. 2013 Jan;42(1):99-105. doi: 10.1111/j.1600-0714.2012.01193.x. Epub 2012 Jul 2.
PAX9 is a transcription factor deeply involved in the gene networks that regulate odontogenesis. To date, only a restricted number of mutations in this gene have been associated with non-syndromic tooth agenesis. Six families segregating non-syndromic oligodontia/hypodontia were screened for mutations in PAX9 gene. A novel missense mutation lying in the exon 2 close to the end of the paired domain in three families was identified. Heterozygous mutation C503G is expected to result in an alanine-to-glycine amino acid change in residue 168 (Ala168Gly), which is invariably conserved among several species. The alanine-glycine change might lead to protein structural alteration because of the unique flexibility properties of glycine. Three mutations in intron 2 were also detected. Variations IVS2-109G>C, IVS2-54A>G, and IVS2-41A>G were identified in both affected and unaffected members of the sample; however, these polymorphic variants may be involved in the phenotype as one proband showing all three intronic mutations in homozygosis was affected with the most severe oligodontia within the sample.
PAX9 是一个转录因子，深度参与调控牙发生的基因网络。迄今为止，只有少数该基因的突变与非综合征性牙齿缺失相关。对六个常染色体显性遗传非综合征性少牙/无牙症家系进行 PAX9 基因突变筛查。在三个家系中，发现临近配对结构域末端的外显子 2 中存在一个新的错义突变。杂合性突变 C503G 预计会导致第 168 位（Ala168Gly）的丙氨酸到甘氨酸氨基酸改变，这种改变在几种物种中是不变的。甘氨酸的独特柔性特性可能导致蛋白质结构发生改变。还检测到 2 号内含子中的三个突变。在受影响和未受影响的样本中均发现了 IVS2-109G>C、IVS2-54A>G 和 IVS2-41A>G 三种变异；然而，这些多态性变体可能与表型有关，因为一个表现出所有三种内含子突变纯合子的先证者在样本中受到最严重的少牙症影响。
