Msx1编码区突变与非综合性唇腭裂相关性分析

Association of mutations in coding regions of Msx1 and nonsyndromic cleft lip with or without cleft palate by DNA sequencing technology

目的:探讨核心家庭中Msx1编码区突变与非综合征性唇腭裂的关系。方法:运用测序技术检测华东地区核心家庭的Msx1基因全部编码区的突变情况,预测其编码氨基酸的突变频率,比较突变位点在患儿与正常儿童中的分布差异并判断是否有统计学意义,比较患者组与父母组的基因型和等位基因频率,并对核心家庭的数据进行单倍型相对风险分析(HRR),对含杂合子父母的核心家庭进行传递不平衡检验(TDT)。结果:Msx1编码区序列共有三个位点突变,分别为编码区1的C101G(A34G)突变,编码区1同义突变C330T(G110G),编码区2的G162A(S278N)突变。其中只有编码区1的同义突变C330T(G110G)在患儿与正常儿童中的分布差异有统计学意义,患者与其父母各位点基因型和等位基因分布差异无统计学意义(P>0.05),HRR结果和TDT结果无统计学意义,另外两个突变位点各项统计均无统计学意义。结论:编码区1的同义突变C330T(G110G)可能与中国华东人群非综合征性唇腭裂存在相关性,而编码区1的C101G(A34G)突变和编码区2的G162A(S278N)突变与中国华东人群非综合征性唇腭裂不存在相关性。

Objective To explore the relationship between mutations in coding regions of Msx1 and nonsyndromic cleft lip with or without cleft palate （NSCL/P）in nuclear families consisting of fathers, mothers and affected offspring with NSCL/P from southeast China, Methods All mutations in coding regions of Msx1 were detected by applying sequencing technology in nuclear families, predicting mutation frequency of amino acid, comparing the distributional difference of affected offspring and unimpaired child and judge that if it has the statistical significance,Then compare the genetype and allele frequency in affected offspring and fathers. Haplotype Relative Risk （HRR） and Transmission Disequilibrium Test （TDT） were performed. Results There were three mutational sites in all ,mutation C101G （A34G） and samesense mutation C330T （G 110G） in coding region1, mutation G 162A （S278N） in coding region2. Only samesense mutation C330T （G110G）in coding region1 has significant difference in genotypes and alleles distribution between patients and normal,No significant difference in genotypes and alleles distribution between patients and their parents, were found. They all got negative results in both HRR and TDT analysis,The other two mutational sites had no significant results in all above. Conclusion There may have some relationship between Samesense mutation C330T （G110G）in coding regionland NSCL/P in population from southeast China but mutation C101G （A34G）in coding regionland mutation G162A（S278N）in coding region2 have no significant relationship in population from southeast China.