家族性腺瘤息肉病家系APC基因C．3925—3929缺失突变分析  

Analysis of C. 3925_3929 deletional mutations of APC gene in pedigrees with familial adenomatous polyposis

作　　者：陈青伟[1] 刘思文[1] 冯继锋[1] 张晓梅[2] 陈森清[2] 马国建[2] 朱明[2] 张元颖[2] 俞军[2] 

机构地区：[1]南京医科大学附属江苏省肿瘤医院内科,210009 [2]江苏省肿瘤防治研究所遗传与分子生物学研究室

出　　处：《中华医学遗传学杂志》2015年第4期524-528,共5页Chinese Journal of Medical Genetics

基　　金：江苏省科教兴卫重点人才基金（RC2011092）;江苏省科技厅重点专项（BL2013035）

摘　　要：目的分析家族性腺瘤息肉病（familial adenomatous polyposis，FAP）家系结肠腺瘤息肉病（adenomatous polyposis coli，APC）基因的突变特点。方法提取13个FAP家系成员外周血DNA，采用多重连接探针扩增（multiplexligation-dependent probe amplification，MLPA）以及PCR扩增，之后直接测序对APC基因进行检测，将测序及MLPA结果与APC基因的野生序列进行比对，寻找各家系成员APC基因的致病性突变。结果共有5个家系筛查出基因突变，分别为C．3184—3187delCAAA、C．5432C〉T、c．3925—3928delAAAA及两个C．3925—3929delAAAAG。小片段缺失突变多处于AAAAG串联重复序列中。结论处于APC基因AAAAG串联重复序列中的C．3925—3929可能为APC基因的突变热点区域，该位点以碱基缺失居多，尤其是密码子1309的5个碱基缺失。Objective To analyze the characteristics of germline mutations of adenomatous polyposis coil （APC） gene in pedigrees affected with familial adenomatous polyposis （FAP）. Methods Genomic DNA was extracted from peripheral blood samples from members of the 13 FAP pedigrees. Multiplex ligation- dependent probe amplification （MLPA） was used to detect large fragment deletions of the APC gene. Subsequently, potential mutation was screened from all exons of the APC gene with PCR amplification and direct sequencing. Results Germline mutations have been identified in 5 FAP pedigrees, which included c, 3184 3187delCAAA, c. 5432C 〉 T, c. 3925_ 3928delAAAA and c. 3925_ 3929del AAAAG （in two pedigrees）. Small deletional mutations were found primarily in the area of AAAAG tandem repeat sequences. Conclusion C. 3920_3929 located in AAAAG tandem repeats is probably the hot spot for APC gene mutations, which are mostly deletional mutations, especially the 5 bp base deletion at codon 1309.

关 键 词：家族性腺瘤息肉病 APC基因 胚系突变 

分 类 号：R735.3[医药卫生—肿瘤]