中国Peutz-Jeghers综合征患者STK11基因突变检测及高频突变分析

摘要

目的 分析Peutz-Jeghers综合征(Peutz-Jeghers syndrome,PJS)患者丝/苏氨酸蛋白激酶11(serine/threonine kinase 11,STK11)基因突变情况,探讨不同STK11基因突变与临床特征的关系.方法 选择完成STK11所有外显子基因测序的患者54例,分析其临床表现及突变分布规律,并比较不同突变间临床特征.结果 54例患者中,33例在STK11基因编码区检测出点突变,先证者30例(检出率58.8%,30/51),家族突变检出率为55.0%(11/20),散发突变检出率为55.9%(19/34).3个家系共5例患者在同一位点突变(c.180C>G),疑为高频突变;另1个家系的2例患者突变位点一致(c.658C>T);1例患者同时检测到2个突变位点;剩余26例患者携带突变各不相同.c.180C>G首次发病年龄和首次手术年龄≤7岁患者中所占比例明显高于其他突变,差异有统计学意义(P<0.05);c.180C>G与其他突变在性别、家族史、肿瘤史、腹部症状、手术史差异均无统计学意义(P>0.05).结论 STK11基因突变是PJS发病的主要致病原因.发现1例可疑为高频突变,该突变患者首次发生症状及接受首次手术年龄均低于其他突变患者,应在临床监测及治疗过程中多予以关注.%Objective To analyze serine/threonine kinase 11 (STK11) gene in patients with Peutz-Jeghers syndrome(PJS), and explore the relationship between different mutations and clinical features.Methods The sequencing of STK11 gene coding region was analyzed from 54 inpatients with PJS.Their clinical manifestations and mutations were analyzed.The clinical characteristics of different mutations were compared.Results Of the 54 patients with PJS, 33 cases were found to have mutations in the coding region of STK11 gene.Among them, 30 cases were probands (the mutation detection rate was 58.8%, 30/51), the mutation detection rate of familial patient was 55.0%(11/20), and the mutation detection rate sporadic patient was 55.9%(19/34).The 5 patients from 3 families had the same point mutation(c.180C>G), which was suspected high frequency mutation.In another family, 2 patients also had the same mutation(c.658C>T).A patient had two mutations;the other 26 patients had a single mutation site.The proportion of patients with c.180C>G in the first onset age and the first surgery age<7 years of age were significantly higher than other mutations, the difference was statistically significant(P<0.05).There were no significant differences in gender, family history, tumor history, abdominal symptoms, and surgical history.Conclusion STK11 gene mutation is the main pathogenicity of PJS.A high frequency mutations were found, patients with this mutation had symptoms and undergo surgery earlier than other patients.We should pay more attention in clinical monitoring and treatment.