Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related to oligodontia.
Next generation sequencing reveals a novel nonsense mutation in MSX1 gene related to oligodontia.
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DOI：
10.1371/journal.pone.0202989
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Šerý O
中科院分区：
文献类型：
--
作者：
Bonczek O;Bielik P;Krejčí P;Zeman T;Izakovičová-Hollá L;Šoukalová J;Vaněk J;Gerguri T;Balcar VJ;Šerý O
牙齿发育不全是人类最常见的颅面疾病之一。超过350个基因与牙齿发育有关。在这项研究中，我们招募了60名患有不同类型牙齿发育不全的儿童患者（年龄在13至17岁之间）。PAX9、MSX1、AXIN2、EDA、EDAR和WNT10a基因全序列在Illumina MiSeq平台上进行下一代测序。我们在一名儿童的MSX1基因中发现了先前未描述的杂合无义突变g.8177G>T （c.610G>T）。突变通过Sanger测序证实。对患儿的其他家庭成员进行测序分析。所有携带g.8177G>T突变的家庭成员均患有少齿症（除第三磨牙外缺失6颗以上牙齿）。突变g.8177G >t导致终止密码子（p.E204X）和Msx1蛋白翻译的过早终止。基于以往对Msx1同源结构域突变破坏功能的体外实验，我们认为g.8177G>T无义突变影响Msx1蛋白的数量和功能，导致牙齿发育。
Tooth agenesis is one of the most common craniofacial disorders in humans. More than 350 genes have been associated with teeth development. In this study, we enrolled 60 child patients (age 13 to 17) with various types of tooth agenesis. Whole gene sequences of PAX9, MSX1, AXIN2, EDA, EDAR and WNT10a genes were sequenced by next generation sequencing on the Illumina MiSeq platform. We found previously undescribed heterozygous nonsense mutation g.8177G>T (c.610G>T) in MSX1 gene in one child. Mutation was verified by Sanger sequencing. Sequencing analysis was performed in other family members of the affected child. All family members carrying g.8177G>T mutation suffered from oligodontia (missing more than 6 teeth excluding third molars). Mutation g.8177G>T leads to a stop codon (p.E204X) and premature termination of Msx1 protein translation. Based on previous in vitro experiments on mutation disrupting function of Msx1 homeodomain, we assume that the heterozygous g.8177G>T nonsense mutation affects the amount and function of Msx1 protein and leads to tooth agenesis.
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