针对尼日利亚人群的基因研究表明，MSX1基因突变与复杂的口腔面部裂缺陷疾病有关。
Genetic studies in the Nigerian population implicate an MSX1 mutation in complex oral facial clefting disorders.
作者信息
Butali A, Mossey P A, Adeyemo W L, Jezewski P A, Onwuamah C K, Ogunlewe M O, Ugboko V I, Adejuyigbe O, Adigun A I, Abdur-Rahman L O, Onah I I, Audu R A, Idigbe E O, Mansilla M A, Dragan E A, Petrin A L, Bullard S A, Uduezue A O, Akpata O, Osaguona A O, Olasoji H O, Ligali T O, Kejeh B M, Iseh K R, Olaitan P B, Adebola A R, Efunkoya E, Adesina O A, Oluwatosin O M, Murray J C
出版信息
Cleft Palate Craniofac J. 2011 Nov;48(6):646-53. doi: 10.1597/10-133. Epub 2011 Jul 8.
BACKGROUND
Orofacial clefts are the most common malformations of the head and neck, with a worldwide prevalence of 1 in 700 births. They are commonly divided into CL(P) and CP based on anatomic, genetic, and embryologic findings. A Nigerian craniofacial anomalies study (NigeriaCRAN) was set up in 2006 to investigate the role of gene-environment interaction in the origin of orofacial clefts in Nigeria.
SUBJECTS AND METHODS
DNA isolated from saliva from Nigerian probands was used for genotype association studies and direct sequencing of cleft candidate genes: MSX1 , IRF6 , FOXE1, FGFR1 , FGFR2 , BMP4 , MAFB, ABCA4 , PAX7, and VAX1 , and the chromosome 8q region.
RESULTS
A missense mutation A34G in MSX1 was observed in nine cases and four HapMap controls. No other apparent causative variations were identified. Deviation from Hardy Weinberg equilibrium (HWE) was observed in these cases (p = .00002). A significant difference was noted between the affected side for unilateral CL (p = .03) and bilateral clefts and between clefts on either side (p = .02). A significant gender difference was also observed for CP (p = .008).
CONCLUSIONS
Replication of a mutation previously implicated in other populations suggests a role for the MSX1 A34G variant in the development of CL(P).
背景
口面部裂隙是头颈部最常见的畸形，全球发病率为每700例出生中有1例。根据解剖学、遗传学和胚胎学研究结果，它们通常分为唇（腭裂）裂（CL(P)）和腭裂（CP）。2006年开展了一项尼日利亚颅面畸形研究（NigeriaCRAN），以调查基因-环境相互作用在尼日利亚口面部裂隙发病中的作用。
对象与方法
从尼日利亚先证者唾液中分离的DNA用于基因型关联研究以及对口面部裂隙候选基因：MSX1、IRF6、FOXE1、FGFR1、FGFR2、BMP4、MAFB、ABCA4、PAX7和VAX1，以及8号染色体q区域进行直接测序。
结果
在9例病例和4个HapMap对照中观察到MSX1基因存在错义突变A34G。未发现其他明显的致病变异。在这些病例中观察到偏离哈迪-温伯格平衡（HWE）（p = 0.00002）。单侧唇（腭裂）裂的患侧与双侧唇（腭裂）裂之间以及两侧唇（腭裂）裂之间存在显著差异（p = 0.03）。腭裂（CP）在性别上也存在显著差异（p = 0.008）。
结论
先前在其他人群中发现的一种突变的重现表明MSX1 A34G变异在唇（腭裂）裂（CL(P)）发生中起作用。
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