Wong Sing-Wai, Liu Hao-Chen, Han Dong, Chang Huai-Guang, Zhao Hong-Shan, Wang Yi-Xiang, Feng Hai-Lan
Department of Prosthodontics, School and Hospital of Stomatology, Peking University, Beijing 100081, China.
Department of Medical Genetics and Peking University Center for Human Disease Genomics, Peking University Health Science Center, Beijing 100191, China and.
Mutagenesis. 2014 Sep;29(5):319-23. doi: 10.1093/mutage/geu019. Epub 2014 Jun 9.
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.304Tyrext48) 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.
少牙症是指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、美观问题和错牙合畸形。Msh 同源盒 1（MSX1）是首个被鉴定出导致非综合征性少牙症的基因。在本研究中，我们在中国一个常染色体显性非综合征性少牙症家系中，鉴定出 MSX1 基因一个新的杂合非终止突变（c.910_911dupTA，p.304Tyrext48）。这个新突变用一个酪氨酸残基替代了终止密码子，可能在 MSX1 的 C 末端增加 48 个氨基酸。进一步的体外研究发现，突变型 MSX1 能够表达，但失去了进入细胞核的能力。这是首次报道表明 MSX1 中的非终止突变导致少牙症。本研究拓宽了 MSX1 的突变谱，并为阐明 MSX1 在牙齿发育不全中的机制提供了新途径。
