Peutz-Jeghers综合征家系的临床特征并LKB1/STK11基因突变分析

Clinical characteristics and LKB1/STK11 gene mutation in a family of Peutz-Jeghers syndrome

目的研究LKB1/STK11基因突变和甲基化在Peutz-Jeghers综合症家系中的作用，分析基因突变类型与临床特征之间的关系。方法收集江苏省肿瘤医院化疗科1例Peutz-Jeghers综合症家系共4名受累成员的外周血和先证者的肠息肉组织，提取相应组织的DNA，采用MLPA、PCR-DNA测序等方法分别检测了胚系和体细胞来源的LKB1/STK11基因大片段缺失、碱基突变、碱基插入和缺失,先证者癌变息肉组织MSP检测基因启动子区域甲基化。结果先证者及其家族受累成员均具有P-J综合征的典型临床表现：消化道的错构瘤性息肉（均经过不同医院的肠镜标本病理验证）和粘膜肢端色素沉着。在先证者和家系受累成员外周血和大肠息肉组织DNA中均发现有病理意义的大片段缺失性突变，在先证者癌变的息肉组织DNA检测到LKB1/STK11基因的甲基化。结论 PJS家族中检测LKB1/STK11基因的胚系突变可作为一种有效的手段来预测风险,基因突变的类型、位点与临床症状间存在密切关系，甲基化状态的改变可能是遗传性PJS息肉发生癌变的重要机制。

Objective To investigate the effects of LKB1/STK11 gene mutation and methylation in Peutz-Jeghers syndrome （PJS）,and to analyze the relationship between the types of gene mutation and clinical characteristics. Methods The peripheral blood of 4 affected members and the intestinal polyp tissue of the proband a family of PJS were collected in the Department of Chemotherapy,Jiangsu Provincial Cancer Hospital. The DNA from the corresponding tissues was extracted. The large deletion,base mutation,base insertion and deletion in the LKB1/STK11 gene originated from the germline and somatic cells were determined by MLPA and PCR-DNA sequencing,respectively. The gene promoter methylation in the cancerous polyp tissue of the proband was determined by MSP. Results The proband and the affected family members had typical clinical manifestations of PJS：the hamartomatous polyps in the digestive tract （all pathological specimens were verified by colonoscopy in different hospitals）and pigmentation at the mucosa. Large deletionof the DNA mutation were found in the peripheral blood and colorectal polyps of the proband and the affected family members,which suggested pathological significance. Methylation of the LKB1/STK11 gene was determined in the cancerous polyp tissue of the proband. Conclusion The detection of LKB1/STK11 gene mutation in the PJS family can be used as an effective method to predict the risk. There is a close relationship between the type and location of gene mutation and clinical symptoms. The change of methylation＆amp;nbsp;status may be an important mechanism of hereditary PJS polyps.