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，是一种复杂的性状，受遗传和环境因素的影响。已有很多研究报道。我们的研究支持BMP4在非综合征性CL/P中的作用，BMP4的突变与微形态和OO相关，多态变异增加了显性CL/P的易感性。最近一项关于IRF6基因变异的研究表明，IRF6增强子AP-2alpha结合位点的变异与唇裂有关。我们之前也报道了NS CL/P与含有TFAP2A基因的6p23区域的连锁关系。我们对TFAP2A及其附近的8个snp进行了基因分型，并使用FBAT进行了传播不平衡测试。在rs1675414中，CL/P与TFAP2A之间存在统计学意义上的相关性（P <0.001）。这些结果支持了TFAP2A变异在口面部裂中的直接作用，并表明对该途径的其他成员的检查和对TFAP2A位点snp的更深入研究可能揭示病因变异。最近的全基因组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中或附近的单核苷酸多态性（snp）进行基因分型。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.