摘要
目的 Peutz-Jeghers综合征是少见的常染色体显性遗传性疾病,患者特征性临床表现为口唇黑斑和肠道多发错构瘤性息肉。LKB1/STK11基因胚系突变与Peutz-Jeghers综合征的发病有密切关系。文中探讨1例Peutz-Jeghers综合征家系LKB1/STK11基因的病理性突变。方法收集家系成员外周血,提取DNA,采用多重连接依赖性探针扩增(multiplex liga-tion-dependent probe amplification,MLPA)、PCR-变性高效液相色谱(denaturing high performance liquid chromatography,DHPLC)、DNA测序等方法分别检测LKB1/STK11基因大片段缺失、碱基突变、碱基插入和缺失。同时收集250名正常人外周血,提取DNA,用PCR-DHPLC筛查验证突变位点在正常人群中的分布。用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。结果家系中2名受累成员均携带LKB1/STK11基因c.924G>C位点的病理性胚系突变,导致Trp308Cys错义突变。结论 LKB1/STK11基因c.924G>C位点的病理性胚系突变是此家系的致病性因素。Peutz-Jeghers综合征家系中LKB1/STK11基因的胚系突变筛查可作为一种有效的手段来预测风险。
Objective Peutz-Jeghers syndrome（PJS） is a rare autosomally dominant gemetic disease,characterized by clinical presentations of lip pigmentation and gastrointestinal hamartomatous polyps,and closely associated with germline mutation of the LKB1/STK11 gene.The aim of this study was to investigate the mutations of the LKB1/STK11 gene in a family with PJS.Methods We detected the LKB1/STK11 gene mutations in the members of a PJS family by systematic screening with multiplex ligation-dependent probe amplification（MLPA） and DNA sequencing.Meanwhile,we also extracted genomic DNA from the peripheral blood of 250 healthy adults,and identified the distribution of mutation sites by denaturing high performance liquid chromatography（PCR-DHPLC）.We analyzed the effects the mutations sites on the structure and function of the coded protein using the SWISS-MODEL software.Results Germline mutation c.924G〉C of LKB1/STK11 was identified only in 2 affected family members,which caused Trp308Cys missense mutation in the protein sequence.Conclusion Identification of the pathogenic germline mutation c.924G〉C of LKB1/STK11 can be used as an effective means to predict the risk factor in a PJS family.
出处
《医学研究生学报》
CAS
北大核心
2012年第9期933-937,共5页
Journal of Medical Postgraduates
