中国人家族性腺瘤性患肉病患者结肠腺瘤性息肉病基因的胚系突变  

Germline mutation of aclenomatous polyposis coil gene in Chinese patients with familial aclenomatous polyposis

作　　者：王婷婷[1] 陈森清[2] 张晓梅[2] 尚俊清[1] 周欣[1] 李金田[2] 周建农[1] 

机构地区：[1]南京医科大学附属江苏省肿瘤医院结直肠外科,210029 [2]江苏省肿瘤防治研究所遗传与分子生物室

出　　处：《中华医学遗传学杂志》2008年第2期199-202,共4页Chinese Journal of Medical Genetics

基　　金：江苏省卫生厅重点医学项目（H2009,H200503）

摘　　要：目的探讨中国人家族性腺瘤性息肉病（familial adenomatous polyposis，FAJP）患者的结肠腺瘤性息肉病（adenomatous polyposis coli，APC）基因的胚系突变类型。方法对9个FAP家系18名成员进行多重连接依赖性探针扩增（multiplex ligation-dependent probe amplification，MLPA）检测APC基因有无大片段缺失。再应用PCR扩增APC基因的15个外显子区域，经变性高效液相色谱（denaturing high performance liquid chromatography，DHPLC）对每个扩增片段进行筛查，流出峰异常的片段，经DNA测序验证小片段的改变。结果9个家系中有3个家系发现有APC基因的胚系突变：家系2为c．3184-3187delCAAA，家系4为c．5432C〉T，家系9为c．3925—3929del AAAAG。3种突变中c．5432C〉T在数据库中未见报道。结论中国人不同的APC基因的胚系突变可引起FAP；无APC胚系突变的FAP患者的发病可能存在其他的机制。Objective To explore the characteristics of adenomatous polyposis coli （APC） gene getmline mutations in Chinese patients with familial adenomatous polyposis （FAP）. Methods Eighteen members from nine FAP pedigrees were studied by using multiplex ligafion-dependent probe amplification（MLPA） to detect large fragment deletion of APC gene. Then, PCR were performed to amplify all exons of APC gene for mutation screening by denaturing high performance liquid chromatography （DHPLC）. When abnormal elufion profile of DHPLC was found, DNA sequencing was performed to determine the mutations. Results Mutations were identified in three pedigrees among the nine pedigrees. They were c.3184 _ 3187 del CAAA in pedigree 2, c.5432C 〉 T in pedigree 4 and c.3925 _ 3929 del AAAAG in pedigree 9 respectively. Among them, c. 5432C 〉 T was novel. Conclusion APC gene germline mutations can cause the development of FAP. The FAP patients without APC gene gennline mutations could be caused by other mechanisms.

关 键 词：家族性腺瘤性息肉病 结肠腺瘤性息肉病基因 胚系突变 

分 类 号：R686[医药卫生—骨科学]