【摘要】 目的了解２９个遗传性非息肉病性结直肠癌（ＨＮＰＣＣ）家系中ｈＭＬＨ１和ｈＭＳＨ２基因的种系突变状况。方法应用ＰＣＲＳＳＣＰ和ＤＮＡ测序的方法进行突变筛选。结果（１）在２９个家系中，ｈＭＬＨ１和ｈＭＳＨ２两个基因的总突变率为３１．０％，与对照组（２％）相比，差异有极显著性（Ｐ＜０．０１），其中ｈＭＬＨ１基因是主要的相关基因。（２）１０名患大肠癌的家系成员均含有与先证者相同的突变，反映了突变与大肠癌的发生之间有很强的相关性。在２９名健康的家系成员中发现了５名突变携带者，为大肠癌的一组高危易感人群。结论错配修复基因的突变筛选可帮助、指导临床对ＨＮＰＣＣ家系进行严密监控更多还原

【Abstract】 Objective To investigate germline mutations of mismatch repair genes hMLH1 and hMSH2 in 29 HNPCC families. Methods Mutations were detected by PCR SSCP analysis, and confirmed by DNA sequencing. Results (1) In 29 families, the overall mutation rate of these two genes was 31.0% (9/29). Mutation detected in all of the 9 families was located in the hMLH1 gene, indicating that the hMLH1 gene was the main responsible gene in these families. An obvious difference was observed when compared to the mutation rate in the control group ( P <0.01); (2) All of the 10 family members who developed colorectal cancer (CRC) harbored the same mutation as detected in their proband, indicating a strong association between gene mutation and development of CRC. In 29 healthy family members, 5 asymptomatic carriers of mutation were found who were considered as the high risk populations of CRC. Conclusion A certain number of HNPCC families can be benefited from the genetic screening for mutation of the mismatch repair genes.更多还原