黑斑息肉综合征STK11基因突变分析  

Mutation analysis of STK11 in a family with Peutz-Jeghers syndrome

作　　者：吴雨虹[1] 邢雪莎[2] 孙忠芙 李丹妮[1] 黄鹤来 罗萍 Wu Yuhong;Xing Xuesha;Sun Zhongfu;Li Danni;Huang Helai;Luo Ping(Cell Biology and Medical Genetic Department, Shenyang Medical College, Shenyang 110046, China;The Research Center for Medical Genomics, China Medical University, Shenyang 110122, China)

机构地区：[1]沈阳医学院细胞与遗传学教研室,110046 [2]中国医科大学医学基因组学教研室,沈阳110122

出　　处：《中国临床实用医学》2019年第1期17-20,共4页China Clinical Practical Medicine

基　　金：沈阳市科技专项资金(F16-206-9-19);沈阳医学院科研基金(20131002);辽宁省博士启动基金(201601137).

摘　　要：目的检测黑斑息肉综合征(PJS)家系丝氨酸/苏氨酸激酶基因11(STK11)基因突变,分析致病机制。方法提取家系中患者及正常人外周血基因组DNA,PCR扩增STK11全部外显子及其侧翼序列,扩增后产物纯化后直接进行DNA测序。结果该家系致病基因突变为STK11第1外显子杂合的碱基置换c.250A>T,为无义突变产生只有84个氨基酸的截短蛋白。结论该家系致病基因突变为c.250A>T(p.K84*),其致病机制为产生的截短蛋白缺失了大部分的激酶催化域,STK11活性下降的同时,p53的活性也明显下降。该致病基因突变具有较高的肿瘤易感风险,建议家系患者定期临床随访。Objective Detecting the serine/threonine kinase ( STK11 ) gene mutation in the PJS family and analyzing the pathogenic mechanism of the detected mutation. Methods The genomic DNA of patients and normal people in the family was extracted from peripheral blood, all exons and flanking se-quences of STK11 were amplified by PCR. The amplified products were directly sequencing. Results The pathogenic mutation of this family was the nonsense mutation(c. 250A>T),which produced a truncated protein of only 84 amino acids. Conclusion The pathogenic mutation in STK11 in this PJS family is c. 250A>T(p. K84?). The pathogenic mechanism is that the truncated protein deletes most of the kinase catalytic domain,resulting in a significant decrease in the activity of p53. This mutation has a high risk of tumor susceptibility,and it is recommended that the patients of this family have regular clinical follow-up.

关 键 词：黑斑息肉综合征 STK11基因 截短蛋白 肿瘤易感风险 

分 类 号：R7[医药卫生—临床医学]