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目的分析Peutz-Jeghers综合征(PJS)家系致病基因的突变。方法收集一个PJS家系成员三代9例的外周血,采用多重连接信赖性探针扩增和PCR-DNA测序方法检测LKB1基因大片段缺失、碱基突变、碱基插入和缺失。同时收集250例正常人外周血,PCR-变性高效液相色谱筛查验证突变位点在正常人群中的分布。生物信息学分析突变位点对编码蛋白质结构和功能的影响。结果先证者及另2例家系受累成员均携带LKB1基因C.48G>T的同义突变,其家系正常人和250例正常人群中无LKB1基因C.48G>T突变位点。生物信息学分析结果显示,此突变可导致新的剪接调控位点产生,使mRNA的剪接发生改变,最终影响蛋白质的结构和功能。结论 C.48G>T位点的突变可能是一种病理性胚系突变,mRNA的剪接调控异常改变可能是此家系的致病性因素。
Objective To analyze the mutations of the causative genes in Peutz-Jeghers syndrome (PJS) pedigrees. Methods Nine peripheral blood samples from three generations of PJS pedigrees were collected. The LKB1 gene deletion, base mutation, base insertion and deletion were detected by multiplex ligation-dependent probe amplification and PCR-DNA sequencing. At the same time, 250 normal human peripheral blood samples were collected and PCR-denaturing high performance liquid chromatography screening was used to verify the distribution of the mutation sites in the normal population. Bioinformatics Analysis of the Effect of Mutation Sites on the Structure and Function of Encoding Proteins. Results The probands and the other 2 affected families carried the synonymous mutation of LKB1 gene C.48G> T. There were no C.48G> T mutation sites in LKB1 gene in 250 healthy controls and normal controls. Bioinformatics analysis results show that this mutation can lead to a new splicing regulatory sites, the mRNA splicing changes, the final impact on protein structure and function. Conclusion The mutation of C.48G> T locus may be a pathogenic germline mutation, which may be the causative factor of this family.