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.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
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)
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
familial adenomatous polypasis
APC gene
germline mutation
denaturing high-performance chromatography
