家族性腺瘤性息肉病家系中一种新的APC基因的胚系突变  

A novel APC gene germline mutation in a familial adenomatous polyposis pedigree

作　　者：周建农[1] 陈森清[2] 张晓梅[2] 周欣[1] 朱明[2] 冯波[3] 李金田[2] 马国建[2] 张元颖[2] 

机构地区：[1]江苏省肿瘤医院普通外科,南京210009 [2]江苏省肿瘤防治研究所遗传与分子生物学室 [3]江苏省肿瘤医院内窥镜室,南京210009

出　　处：《中华医学遗传学杂志》2006年第4期388-391,共4页Chinese Journal of Medical Genetics

基　　金：江苏省卫生厅重点医学项目(H2009;H200142)

摘　　要：目的研究1个家族性腺瘤性息肉病家系的腺瘤样息肉病基因(adenomatouspolyposiscoli,APC)的胚系突变。方法经结肠镜、组织病理学检查和家族史的调查,确定了1例家族性腺瘤性息肉病(familialadenomatouspolyposis,FAP)患者。应用多重连接依赖性探针扩增(multiplexligation-dependentprobeamplification,MLPA)、变性高效液相色谱(denaturinghigh-performanceliquidchromatography,DHPLC)和测序等技术对这一家系的成员进行系统的APC全基因筛查。结果在此家系中发现一个新的APC基因的胚系突变c.1999C>T(Q667X),这一突变造成了APC基因终止密码子的形成,从而形成有功能障碍的截短蛋白。临床上,此突变可引起严重的FAP症状,早发结直肠腺瘤和腺癌。结论Q667X胚系突变是引起该家系临床表型的原因,受累成员可考虑大肠预防性切除手术。Objective To detect the adenomatous polyposis coli （APC） gene germline mutation in the proband and her family members with familial adenomatons polyposis （FAP）. Methods The diagnosis of a patient with FAP was validated by colonscopy, pathology and the family history. The systematic screening with multiplex ligation-dependent probe amplification （MLPA）, denaturing high-performance liquid chromatography （DHPLC） and DNA sequencing were carried out to detect APC gene germline mutations. Results A novel mutation c. 1999 C 〉 T （Q667X） of APC, which leads to premature termination of the protein, was identified in this family. This mutation manifested an aggressive form of FAP with early onset of colorectal adenocarcinoma and colonic adenoma. Conclusion The mutation of APC Q667X is the cause of clinical phenotype of this family with FAP, and the prophylactic colectomy for the affected family members should be considered.

关 键 词：家族性腺瘤性息肉病 APC基因 胚系突变 变性高效液相色谱 

分 类 号：R735.3[医药卫生—肿瘤]