A novel non-stop mutation in MSX1 causing autosomal dominant non-syndromic oligodontia
A novel non-stop mutation in MSX1 causing autosomal dominant non-syndromic oligodontia
复制标题
MSX1 中一种新型不间断突变导致常染色体显性非综合征性少牙症
DOI：
10.1093/mutage/geu019
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发表时间：
2014-09-01
期刊：
影响因子：
2.7
通讯作者：
Feng, Hai-Lan
中科院分区：
文献类型：
--
作者：
Wong, Sing-Wai;Liu, Hao-Chen;Feng, Hai-Lan
少齿症是先天性缺失六颗或更多恒牙，不包括第三磨牙，可能导致咀嚼功能障碍，言语改变，美学问题和咬合不正。Msh同源框1（MSX1）是第一个被鉴定为引起非综合征性少牙症的基因。在这项研究中，我们发现了一种新的杂合非终止突变（c.910_911dupTA，p.* 304Tyrext*48）在一个中国常染色体显性遗传非综合征性少牙症家系MSX1中的表达。这种新的突变用酪氨酸残基取代了终止密码子，可能在MSX1的C末端添加了48个氨基酸。进一步的体外研究发现，突变体MSX1可以表达，但失去了进入细胞核的能力。这是第一份报告表明MSX1的非终止突变是导致少牙症的原因。本研究拓宽了MSX1的突变谱，为阐明MSX1在牙齿发育不全中的作用机制提供了新的思路。
Oligodontia, which is the congenital absence of six or more permanent teeth, excluding the third molars, may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. Msh homeobox 1 (MSX1) was the first gene identified as causing non-syndromic oligodontia. In this study, we identified a novel heterozygous non-stop mutation (c.910_911dupTA, p.*304Tyrext*48) in MSX1 in a Chinese family with autosomal dominant non-syndromic oligodontia. This novel mutation substitutes the stop codon with a tyrosine residue, potentially adding 48 amino acids to the C-terminus of MSX1. Further in vitro study found that mutant MSX1 could be expressed but had lost its ability to enter the nucleus. This is the first report indicating that a non-stop mutation in MSX1 is responsible for oligodontia. This study broadens the mutation spectrum for MSX1 and provides a new way to clarify the mechanism of MSX1 in tooth agenesis.