Mutations in WNT10A are present in more than half of isolated hypodontia cases
Mutations in WNT10A are present in more than half of isolated hypodontia cases
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DOI：
10.1136/jmedgenet-2012-100750
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发表时间：
2012-05-01
影响因子：
4
通讯作者：
van Amstel, Hans Kristian Ploos
中科院分区：
文献类型：
--
作者：
van den Boogaard, Marie-Jose;Creton, Marijn;van Amstel, Hans Kristian Ploos
背景牙齿发育不全是人类最常见的、可遗传的发育异常。在家族性严重牙齿发育不全中检测到MSX 1、PAX 9、AXIN 2和外胚层发育不良基因EDA、EDAR和EDARADD的突变。然而，直到最近，在大多数情况下（约90%），遗传因素无法确定，这意味着其他基因必须参与。WNT 10A在牙齿发育中的作用以及WNT 10A突变导致的常染色体隐性遗传病--牙突胚层发育不良携带者的缺牙症的发现（OMIM 257980;方法对34例先天性缺牙患者的WNT 10 A基因、MSX 1、PAX 9、IRF 6和AXIN 2已被测序。先证者均为6 ~ 28颗牙的孤立性缺牙。结果在56%的非综合征性缺牙病例中发现了WNT 10A基因突变。MSX 1、PAX 9和AXIN 2突变分别占3%、9%和3%。结论WNT 10A基因是引起孤立性缺牙的主要基因。通过将WNT 10A包括在孤立牙齿发育不全的DNA诊断中，在这种条件下的分子检测的产率从15%显著增加到71%。
Background Dental agenesis is the most common, often heritable, developmental anomaly in humans. Mutations in MSX1, PAX9, AXIN2 and the ectodermal dysplasia genes EDA, EDAR and EDARADD have been detected in familial severe tooth agenesis. However, until recently, in the majority of cases (similar to 90%) the genetic factor could not be identified, implying that other genes must be involved. Recent insights into the role of Wnt10A in tooth development, and the finding of hypodontia in carriers of the autosomal recessive disorder, odontooncychodermal dysplasia, due to mutations in WNT10A (OMIM 257980; OODD), make WNT10A an interesting candidate gene for dental agenesis.Methods In a panel of 34 patients with isolated hypodontia, the candidate gene WNT10A and the genes MSX1, PAX9, IRF6 and AXIN2 have been sequenced. The probands all had isolated agenesis of between six and 28 teeth.Results WNT10A mutations were identified in 56% of the cases with non-syndromic hypodontia. MSX1, PAX9 and AXIN2 mutations were present in 3%, 9% and 3% of the cases, respectively.Conclusion The authors identified WNT10A as a major gene in the aetiology of isolated hypodontia. By including WNT10A in the DNA diagnostics of isolated tooth agenesis, the yield of molecular testing in this condition was significantly increased from 15% to 71%.