Wang Y, Friedl W, Propping P
Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210009 P.R. China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1998 Dec 10;15(6):333-6.
Analysis for germline mutation in mismatch repair genes, hMLH1 and hMSH2, in hereditary nonpolyposis colorectal cancer (HNPCC) patients and presymptomatic diagnosis in HNPCC families.
Genomic DNA extracted from peripheral blood were subjected to mutation analysis in 35 exons of the hMLH1 and hMSH2 genes by heteroduplex and single strand conformation polymorphism(SSCP) followed by DNA sequencing of aberrant bands in 14 HNPCC and 10 colorectal cancer patients with familial history.
Germline mutations were identified in 4/14 HNPCC patients and in 1/10 colorectal cancer patients with familial history, 2 of them in the hMLH1 and 3 in hMSH2 genes. The five mutations are all unique and are predicted to result in nonfunctional proteins by either frameshift (three), nonsense (one) or missense mutation (one) in evolutionarily conserved region.
HNPPC is closely related to the mutations of mismatch repair genes. Germline mutation analysis for presymptomatic diagnosis in HNPCC could not be limited in the patients meeting clinical diagnosis criteria (Amsterdam 1991).
分析遗传性非息肉病性结直肠癌（HNPCC）患者错配修复基因hMLH1和hMSH2中的种系突变，并对HNPCC家系进行症状前诊断。
从14例HNPCC患者和10例有家族史的结直肠癌患者的外周血中提取基因组DNA，采用异源双链和单链构象多态性（SSCP）方法对hMLH1和hMSH2基因的35个外显子进行突变分析，随后对异常条带进行DNA测序。
在14例HNPCC患者中的4例以及10例有家族史的结直肠癌患者中的1例中鉴定出种系突变，其中2例发生在hMLH1基因，3例发生在hMSH2基因。这五个突变均为独特突变，预计通过移码突变（三个）、无义突变（一个）或错义突变（一个）在进化保守区域导致无功能蛋白。
HNPPC与错配修复基因的突变密切相关。对HNPCC进行症状前诊断的种系突变分析不能局限于符合临床诊断标准（1991年阿姆斯特丹标准）的患者。
