中文摘要：

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。

英文摘要：

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.