Modesto A, Moreno L M, Krahn K, King S, Lidral A C
Dows Institute for Dental Research, College of Dentistry, University of Iowa, IA 52242, USA.
J Dent Res. 2006 Jun;85(6):542-6. doi: 10.1177/154405910608500612.
MSX1 has been considered a strong candidate for orofacial clefting, based on mouse expression studies and knockout models, as well as association and linkage studies in humans. MSX1 mutations are also causal for hereditary tooth agenesis. We tested the hypothesis that individuals with orofacial clefting with or without tooth agenesis have MSX1 coding mutations by screening 33 individuals with cleft lip with or without cleft palate (CL/P) and 19 individuals with both orofacial clefting and tooth agenesis. Although no MSX1 coding mutations were identified, the known 101C > G variant occurred more often in subjects with both CL/P and tooth agenesis (p = 0.0008), while the *6C-T variant was found more often in CL/P subjects (p = 0.001). Coding mutations in MSX1 are not the cause of orofacial clefting with or without tooth agenesis in this study population. However, the significant association of MSX1 with both phenotypes implies that MSX1 regulatory elements may be mutated.
基于小鼠表达研究、基因敲除模型以及人类的关联和连锁研究，MSX1被认为是口面裂的一个强有力的候选基因。MSX1突变也是遗传性牙齿缺失的病因。我们通过筛查33例唇裂伴或不伴腭裂（CL/P）患者以及19例既有口面裂又有牙齿缺失的患者，来检验以下假设：患有或不患有牙齿缺失的口面裂患者存在MSX1编码突变。尽管未鉴定出MSX1编码突变，但已知的101C>G变异在既有CL/P又有牙齿缺失的受试者中出现得更频繁（p = 0.0008），而*6C-T变异在CL/P受试者中更常见（p = 0.001）。在本研究人群中，MSX1的编码突变不是导致有或没有牙齿缺失的口面裂的原因。然而，MSX1与这两种表型的显著关联意味着MSX1调控元件可能发生了突变。
