Novel MSX1 variants identified in families with nonsyndromic oligodontia.
Novel MSX1 variants identified in families with nonsyndromic oligodontia.
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在非综合征性少牙症家族中发现新的 MSX1 变异
DOI：
10.1038/s41368-020-00106-0
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发表时间：
2021-01-08
影响因子：
14.9
通讯作者：
Han D
中科院分区：
文献类型：
--
作者：
Zheng J;Yu M;Liu H;Cai T;Feng H;Liu Y;Han D
本研究的目的是确定MSX1基因变异在多个中国家庭与非综合征性少牙，并分析这些变异的功能影响。对5个非综合征性少牙症家系进行全外显子组测序（WES）和桑格测序，并利用一系列生物信息学数据库进行变异确认和功能预测。这些家庭的成员的表型特征进行了描述，并在体外分析进行功能评价。鉴定了五种新的MSX1杂合变体：三种错义变体[c.662A>C（p.Q221P）、c.670C>T（p.R224C）和c.809C>T（p.S270L）]，一种无义变体[c.364G>T（p.G122*）]和一种移码变体[c.277delG（p.A93Rfs*67）]。初步体外研究表明，与野生型相比，MSX1的亚细胞定位在p.Q221P、p.R224C、p.G122* 和p.A93Rfs*67变体中是异常的。三种变体（p.Q221P、p.G122* 和p.A93Rfs*67）被归类为致病性或可能致病性，而p.S270L和p.R224C在当前数据中的意义不确定。此外，我们总结和分析了MSX1相关的牙齿发育不全的位置，发现类型和变异位点与牙齿缺失的严重程度无关。我们的研究结果扩大了非综合征性少牙症的变异谱，并为遗传咨询提供了有价值的信息。
The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.
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影响因子：
3.7
作者：
Bonczek O;Bielik P;Krejčí P;Zeman T;Izakovičová-Hollá L;Šoukalová J;Vaněk J;Gerguri T;Balcar VJ;Šerý O
通讯作者：
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影响因子：
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作者：
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通讯作者：
Trzeciak, WH
影响因子：
3
作者：
Mostowska, Adrianna;Biedziak, Barbara;Jagodzinski, Pawel P.
通讯作者：
Jagodzinski, Pawel P.