Toward an orofacial gene regulatory network.
Toward an orofacial gene regulatory network.
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DOI：
10.1002/dvdy.24341
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Schutte BC
中科院分区：
文献类型：
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作者：
Kousa YA;Schutte BC
口面裂是一种常见的出生缺陷，发病率高。通过动物模型和人类遗传学的协同作用，已经发现了一系列候选基因。其中，干扰素调节因子6（IRF 6）的变异导致综合征性口面裂，并导致孤立性唇腭裂的风险（1/700活产）。IRF 6的罕见变异可导致货车德沃德综合征（1/35，000活产）和腘翼状胬肉综合征（1/300，000活产）。此外，IRF 6调节GRHL 3，并且该下游靶标中的罕见变体也可导致货车德沃德综合征。此外，IRF 6基因座的一个常见变异（rs642961）在世界30%的人口中发现，并导致孤立性口面裂的风险。生化研究表明，rs642961废除了四个AP-2 α结合位点之一。与IRF 6和GRHL 3一样，TFAP 2A中的罕见变体也可导致具有唇凹的综合征性口面裂（鳃-眼-面综合征）。文献表明，AP-2 α，IRF 6和GRHL 3是唇和腭发育所必需的途径的一部分。除了更新的途径，球员和追求，这篇评论将突出一些当前的问题，在研究口面裂。
Orofacial clefting is a common birth defect with significant morbidity. A panoply of candidate genes have been discovered through synergy of animal models and human genetics. Among these, variants in Interferon Regulatory Factor 6 (IRF6) cause syndromic orofacial clefting and contribute risk toward isolated cleft lip and palate (1/700 live births). Rare variants in IRF6 can lead to Van der Woude Syndrome (1/35,000 live births) and Popliteal Pterygium Syndrome (1/300,000 live births). Furthermore, IRF6 regulates GRHL3 and rare variants in this downstream target can also lead to Van der Woude Syndrome. In addition, a common variant (rs642961) in the IRF6 locus is found in 30% of the world’s population and contributes risk for isolated orofacial clefting. Biochemical studies revealed that rs642961 abrogates one of four AP-2alpha binding sites. Like IRF6 and GRHL3, rare variants in TFAP2A can also lead to syndromic orofacial clefting with lip pits (Branchio-oculo-facial Syndrome). The literature suggests that AP-2alpha, IRF6 and GRHL3 are part of a pathway that is essential for lip and palate development. In addition to updating the pathways, players and pursuits, this review will highlight some of the current questions in the study of orofacial clefting.