Recent genetics of Cleft Lip and Palate

非综合征性唇裂伴或不伴腭裂(CL/P)是一种常见的出生缺陷，是一种受遗传和环境因素影响的复杂性状。已经有很多研究报道过。我们的研究支持BMP4在非综合征性CL/P中的作用，BMP4的突变与微型体和OO相关，多态变异增加了对显性CL/P的易感性。最近对IRF6基因变异的研究表明，IRF6增强子中AP-2α结合位点的变异与唇裂有关。我们以前也报道过NS CL/P与含有TFAP2A基因的6p23区域连锁。我们对TFAP2A及其附近的8个SNPs进行了基因分型，并用FBAT进行了传递不平衡检验。在rs1675414位点上，CL/P和TFAP2a(p&lt；0.001)之间有统计学意义的相关性。这些结果支持TFAP2A基因变异在口裂发生中的直接作用，并提示对该通路其他成员的检查和对TFAP2A基因SNPs的深入研究可能揭示病因学变异。最近的基因组广泛关联研究也发现了多个基因座，如MAFB、VAX1和PAX7。我们对VAX1、MAFB和PAX7及其附近的单核苷酸多态(SNPs)进行了基因分型。结果表明，这些基因与唇腭裂有很强的相关性。

Nonsyndromic cleft lip with or without cleft palate (CL/P), a common birth defect, is a complex trait, arising from the influence of genetic and environmental factors. There are many studies have been reported. Our study supports the role of BMP4 in nonsyndromic CL/P, with mutations in BMP4 associated with microforms and OO, and polymorphic variants increasing the susceptibility to overt CL/P.A recent study of variants in the IRF6 gene showed variants in an AP-2alpha binding site in an IRF6 enhancer is associated with cleft lip. We have also previously reported the linkage of NS CL/P to the 6p23 region that contains TFAP2A gene. We genotyped 8 SNPs in and near TFAP2A and FBAT was used for transmission disequilibrium test. A statistically significant association between CL/P and TFAP2A (p<0.001) was shown for rs1675414. These results support a direct role for variation of TFAP2A in orofacial clefting and suggests that examination of additional members of this pathway and deeper investigation of SNPs at the TFAP2A locus may disclose etiologic variants. Also recent Genome wide associations study discovered multiple loci such as MAFB, VAX1 and PAX7. We genotyped single nucleotide polymorphisms (SNPs) in or near VAX1, MAFB and PAX7. Results showed strong association between these genes and cleft lip and palate.