Isolated Oligodontia Associated With Mutations in EDARADD, AXIN2, MSX1, and PAX9 Genes
Isolated Oligodontia Associated With Mutations in EDARADD, AXIN2, MSX1, and PAX9 Genes
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DOI：
10.1002/ajmg.a.34045
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发表时间：
2011-07-01
影响因子：
2
通讯作者：
Dahl, Niklas
中科院分区：
文献类型：
--
作者：
Bergendal, Birgitta;Klar, Joakim;Dahl, Niklas
少齿症是指先天性缺少六颗或六颗以上的恒牙，不包括第三磨牙。少齿症和缺齿症（缺少一颗或多颗恒牙）是与AXIN 2、MSX 1、PAX 9、EDA和EDAR基因突变相关的高度遗传性疾病。在此，我们确定了93名非综合征性孤立性少牙症瑞典先证者队列中AXIN 2、MSX 1、PAX 9、EDA和EDAR基因以及新候选基因EDARADD突变的患病率。采用变性梯度凝胶电泳和DNA序列分析进行突变筛选。对6个基因编码序列的分析显示，93个先证者中有10个（10.8%）的序列改变被预测为具有损害性或潜在损害性。分别在EDARADD（n = 1）、AXIN 2（n = 3）、MSX 1（n = 2）和PAX 9（n = 4）基因中发现了突变。10个有突变的先证者中没有一个有来自外胚层组织的其他自我报告的症状。口腔参数是相似的，当比较个人和没有突变，但少齿症的家族史是三倍更频繁的突变先证者。EDARADD突变以前曾报道在一些家庭隔离少汗性外胚层发育不良，这是，据我们所知，第一次报告的EDARADD突变与孤立的少牙。(C)2011 Wiley-Liss，Inc.
Oligodontia is defined as the congenital lack of six or more permanent teeth, excluding third molars. Oligodontia as well as hypodontia (lack of one or more permanent teeth) are highly heritable conditions associated with mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes. Here we define the prevalence of mutations in the AXIN2, MSX1, PAX9, EDA, and EDAR genes, and the novel candidate gene EDARADD in a cohort of 93 Swedish probands with non-syndromic, isolated oligodontia. Mutation screening was performed using denaturing gradient gel electrophoresis and DNA sequence analysis. Analyses of the coding sequences of the six genes showed sequence alterations predicted to be damaging or potentially damaging in ten of 93 probands (10.8%). Mutations were identified in the EDARADD (n = 1), AXIN2 (n = 3), MSX1 (n = 2), and PAX9 (n = 4) genes, respectively. None of the 10 probands with mutations had other self-reported symptoms from ectodermal tissues. The oral parameters were similar when comparing individuals with and without mutations but a family history of oligodontia was three times more frequent for probands with mutations. EDARADD mutations have previously been reported in a few families segregating hypohidrotic ectodermal dysplasia and this is, to our knowledge, the first report of an EDARADD mutation associated with isolated oligodontia. (C) 2011 Wiley-Liss, Inc.