Development of the diagnostic methods for the intrinsic factor of the maxillo-facial deformity using HLA and the related genes

颌面部畸形、唇腭裂和鳃弓综合征的病因复杂，既有遗传因素，也有环境因素。然而，迄今为止，还没有确定这些疾病的特定遗传因素。对于这些畸形，每次手术和正畸治疗都很难取得良好的效果。因此，从预防的角度，包括临床基因治疗，我们必须了解这些疾病的发病机制和相关基因。然后，作为第一步，我们确定先前在患有唇裂、腭裂或两者的受试者中研究的候选基因是否与HLA-DRB 1 ^*1302（位于HLA中的外显子2）（（实验1））和同源框基因DLX 1和DLX 2相关。（（实验二））对象：实验一为一百一十二名被试，一百四十五名对照。方法：实验1采用PCR-MPH方法，实验2采用PCR-Direct测序方法，对候选基因进行基因型分析。结果：实验1中总CL/P与HLA-DRB 1 ^*1301和HLA-DRB 1 ^*1302（与非腭裂对照组相比）呈正相关。同时，右CL/P与HLA-DRB 1 ^*0802和^*1202之间存在疑似关联。实验二在DLX 1的翻译区未发现常见的突变，但在DLX 2的外显子1上发现了与（AGC）n相关的突变，提示HLA和DLX 2基因可能参与了裂殖的形成，并决定了裂殖的类型和部位。

The maxillo-facial deformities, orofacial clefting and branchial arch syndromes are considered to be causesd by complex etiology, including both genetic and enxironmental factors. To date, however no particular genetic factors has been confiremed for these diseases. It is very difficult to get good results of surgical and orthodontic treatment for these malformation everytime. So from a preventive point of view, including the clinical genetic treatment, we must get infomations of mechanism for causing these diseases and related genes. Then, as a first step, we determine whether the candidate genes previously studied in subjects with cleft lip, cleft palate, or both are associated with HLA-DRB1^*1302 (located exon2 iin HLA) ((Experiment 1)) and homeobox gene, DLX1 and DLX2.((Experiment 2))Subject: One hundred twelve subjects, and one hundred forty-five controls for Experiment 1. One hundred forty -two subjects, and ninety-six controls for Experiment 2Method: Genotype analysis of candidate genes was performed using PCR-MPH method for Exp.1 and PCR-Direct sequenseanalysis fo Exp.2.Result: Positive association between subjects with total-CL/P and HLA-DRB1^*1301 and HLA-DRB1^*1302 (compared with noncleft controls) was found in Experiment 1. And at the same time, there was a susupective association between subjects with right-CL/P and HLA-DRB1^*0802,and ^*1202. In Exp.2, we couldn't identify commom mutaons in translated region on DLX1, but there was a suspective association between subjects with complete-CUP and (AGC)n in exonl on DLX2.These result suspect that HLA and DLX2 gene associate for forming of clefting, and for determine the type and location of clefting.