摘要
目的研究家族性Peutz-Jeghers综合征患者中LKB1基因胚系突变特征。方法收集11个Peutz—Jeghers综合征家系，各家系先证者均有典型的黏膜黑斑以及肠道错构瘤性息肉。提取先证者外周血DNA，PCR扩增LKB1基因的9个外显子及其侧翼的部分内含子序列，测序并分析其变异情况和突变性质。收集250名正常人外周血并提取DNA，聚合酶链反应-变性高效液相色谱筛查验证。结果11个家系先证者中有8例患者LKB1基因外显子及侧翼碱基序列存在杂合性变异，变异类型共9种，包括7种点突变，1种外显子区域小片段碱基缺失以及1种侧翼内含子小片段碱基插入。其中4种考虑为病理性突变，还有4种仅为基因多态性表现，另外有1种变异性质未定。结论LKB1基因病理性突变是中国人家族性Peutz-Jeghers综合征患者的常见病因，且以点突变为主。
Objective To screen for potential mutations of LKB1 gene in Chinese familial PeutzJeghers syndrome （PJS） patients and analyze their clinical manifestations. Methods Eleven PJS families were collected and genomie DNA of peripheral blood was extracted. Typically mucosal pigmentation and hamartomatous polyps were present in all 11 probands. Mutation screening of the probands were carried out by PCR and direct sequencing. Two hundred and fifty healthy adults were enrolled as normal controls, for whom genomic DNA of peripheral blood was also extracted. PCR-denaturing high performance liquid chromatography was carried out to verify the mutation identified in the patients. Results Nine germline mutations were identified in eight PJS patients, which included 7 point mutations, 1 deletion and 1 insertion. Among these, 4 were considered to be pathogenic, of which 2 were de novel, 4 were considered to be polymorphism, and 1 was uncertain. Conclusion LKB1 gene mutations with pathogenic effect are a common cause of familial PJS in Chinese patients. Most mutations are point mutations.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2012年第2期121-125,共5页
Chinese Journal of Medical Genetics
基金
基金项目：南京军区南京总医院科研基金（2009M002）
