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目的通过分析遗传性非息肉性大肠癌（ＨＮＰＣＣ）患者错配修复基因的遗传性突变，对患者的家族成员进行遗传咨询和症状前的基因诊断。方法用ＰＣＲ－异源双链体形成、ＰＣＲ－ＳＳＣＰ和ＤＮＡ序列分析技术，检测１４例ＨＮＰＣＣ、１０例有家族史大肠癌患者的外周血细胞ＤＮＡ，分析其错配修复基因ｈＭＬＨ１、ｈＭＳＨ２的所有３５个外显子。结果确认４／１４的ＨＮＰＣＣ、１／１０有家族史的大肠癌患者携带遗传性错配修复基因的突变，其中２例见于ｈＭＬＨ１基因，３例ｈＭＳＨ２基因。突变类型：３例由碱基缺失导致的移码突变，１例无义突变，１例错义突变。结论ＨＮＰＣＣ的发生与错配修复基因的突变密切相关；在大肠癌患者中检测遗传性错配修复基因的突变不宜仅限于严格符合临床诊断标准的ＨＮＰＣＣ患者。
Objective To analyze genetic mutations of mismatch repair genes in hereditary non-polyposis colorectal cancer (HNPCC) patients and to perform genetic counseling and pre-symptomatic genetic diagnosis on family members. METHODS: PCR-heteroduplex formation, PCR-SSCP and DNA sequence analysis techniques were used to detect peripheral blood cell DNA in 14 patients with HNPCC and 10 patients with family history of colorectal cancer. All of the mismatch repair genes hMLH1 and hMSH2 were analyzed. Exons. The results confirmed that 4/14 of HNPCC, 1/10 of patients with family history of colorectal cancer carrying genetic mismatch repair mutations, of which 2 cases were found in the hMLH1 gene, 3 cases of hMSH2 gene. Mutation types: 3 frameshift mutations due to base deletion, 1 nonsense mutation, and 1 missense mutation. Conclusion The occurrence of HNPCC is closely related to the mutation of mismatch repair genes. Detection of genetic mismatch repair mutations in patients with colorectal cancer should not be limited to HNPCC patients who strictly meet the clinical diagnostic criteria.