两个遗传性非息肉性结直肠癌家系中MLHl和MSH2基因的突变检测  

Mutation screening of MLH1 and MSH2 genes in two Chinese families with hereditary nonpolyposis colorectalcancer

作　　者：谢志国[1] 胡正茂[1] 龚惠勇[1] 凌捷[1] 莫晓云[1] 张静[1] 潘乾[1] 龙志高[1] 戴和平[1] 梁德生[1] 邬玲仟[1] 夏昆[1] 

机构地区：[1]中南大学医学遗传学国家重点实验室,长沙410078

出　　处：《中华医学遗传学杂志》2008年第2期221-224,共4页Chinese Journal of Medical Genetics

基　　金：国家973项目（2004CB518601）;国家自然科学基金（30371530,30600247）

摘　　要：目的确定两个遗传性非息肉性结直肠癌（hereditary nonpolyposis colorectal cancer，HNPCC）家系的致病基因，选择MLHl基因和MSH2基因进行突变检测。方法采用聚合酶链反应结合DNA直接测序法，对两个遗传性非息肉性结直肠癌家系的患者进行MLHl基因和MSH2基因的突变检测；发现变异后，采用PCR-限制性片段长度多态性或直接测序法鉴定此变异是否属于突变。结果在家系A的患者中发现了位于MLHl基因第3外显子内的新突变c．243_244insA；在家系B的患者中发现了MSH2基因第7外显子内的c．1215_1218dupCCGA突变，这两个突变都导致了编码蛋白的提前终止。结论MLHl基因的c．243_244insA突变和MSH2基因的c．1215_1218dupCCGA突变分别是导致家系A和家系B发生遗传性非息肉性结直肠癌的致病突变。Objective To identify the MLH1 and MSH2 gene mutation in two hereditary nonpelyposis colorectal cancer （HNPCC） families. Methods Polymerase chain reaction and DNA sequencing were used to screen for MLH1 and MSH2 gene mutation, and PCR-restriction fragment length polymorphism and DNA sequencing were performed to confirm the mutation. Results By DNA sequencing, a novel mutation of c. 243 _ 244insA located at the exon 3 of MLH1 gene was detected in family A, while c. 1215 _ 1218dupCCGA mutation located at the exon 7 of MSH2 gene was detected in family B. These two mutations can cause the formation of premature proteins. Conclusion The novel mutations c. 243 _ 244insA in MLH1 gene and c. 1215 _ 1218dupCCGA in MSH2 gene were the disease-causing mutations in the two HNPCC families.

关 键 词：遗传性非息肉性结直肠癌 MLHl基因 MSH2基因 

分 类 号：R686[医药卫生—骨科学]