家族性腺瘤性息肉病一家系调查及APC基因胚系突变分析  

Pedigree analysis and study of germline mutations in the APC gene in a kindred with familial adenomatous polyposis

作　　者：武治国[1] 陈明清[1] 董坚[2] 彭勇[1] 毛剑锋[1] 王苗[2] 

机构地区：[1]昆明医学院第一附属医院肿瘤治疗中心,650032 [2]昆明医学院第一附属医院生物治疗中心,650032

出　　处：《国际遗传学杂志》2010年第2期117-121,共5页International Journal of Genetics

基　　金：云南省社会发展科技计划基金资助项目（2007CA009）

摘　　要：目的探讨家族性腺瘤性息肉病（familial adenomatous polyposis，FAP）家系调查及高危亲属基因筛查的意义，报道云南省一FAP家系发病相关基因APC基因的胚系突变结果。方法查阅对2001年昆明医学院第一附属医院1例FAP患者病例，电话联系及登门随访进行其家系调查，绘制家系图谱。抽取该家系成员外周静脉血提取DNA，利用PCR方法扩增APC基因，应用DNA自动测序仪进行测序。结果该家系三代共计9人，成员Ⅰ1、Ⅱ1、Ⅱ2、Ⅱ3、Ⅱ4、Ⅲ2、Ⅲ3、Ⅲ4 8人检出APC基因胚系突变c．3587C〉A（S1196X），其中Ⅱ2、Ⅱ3、Ⅱ4、Ⅲ2、Ⅲ3经肠镜检查证实有结直肠多发息肉，Ⅲ4未检出息肉，为基因突变携带者。结论通过家系调查对高危亲属进行基因筛查可以发现早期患者，尤其是无临床表现的FAP基因突变携带者，以早期进行医学干预及预防性手术治疗，降低FAP的癌变率、病死率；APC基因c．3587C〉A（S1196X）胚系突变是引起该家系FAP患者发病的原因。Objective To explore the significance of pedigree analysis and gene screening for the atrisk membership of a kindred with familial adenomatous polyposis （ FAP）, and to report the results of germline mutations in the APC gene that predispose the disease susceptibility in the kindred with FAP from Yunnan Province. Methods Using a patient with FAP as index patient, the pedigree and all lineal and collateral relatives were interviewed, and then pedigree was protracted. Genomic DNA was extracted from the peripheral blood leukocytes of individuals from the family and the APC gene was screened for germline mutations by using PCR and DNA direct sequencing. Results Among the nine individuals subjected to genetic analysis of the APC gene from the family, mutation was detected in eight, which is the C to A transversion resulting in a stop codon at codon 1196（ TCA 〉 TAA ,c. 3587C 〉 A） within exon 15. Family members Ⅱ 2, Ⅱ 3, Ⅲ4, Ⅲ2,Ⅲ3 were found positive for multiple polyps using colonoscopy. Ⅲ 4 was a gene mutation carrier but does not have any polyps. Conclusion Patient with FAP can be diagnosed early by genetic counseling and thus gene screening for the at-risk relatives in FAP family. It is very helpful in particular for the APC gene mutation carriers and pre-symptomatic. Preventive treatment can be done to reduce the rate of malignant transformation and mortality of FAP. In this study, genomic mutation （p. S1196X） of the APC was confirmed to be pathogenic, which was similar to the previous reports in other areas.

关 键 词：家族性腺瘤性息肉病 APC基因 家系调查 胚系突变 

分 类 号：R7[医药卫生—临床医学]