回族Lynch综合征一家系错配修复基因表达及突变情况分析

Pedigree analysis and gene mutation inspection of Lynch syndrome in Hui nationality

目的分析回族Lynch综合征一家系错配修复基因(MMR)表达及突变情况,探讨回族Lynch综合征的基因特点。方法先证者男性,37岁,第4代,回族,直肠低分化腺癌。本家系现存6代(均为回族),共有结直肠癌患者14例,在世7例。提取本家系中6例患者及5例正常人外周血及肿瘤组织DNA。采用DNA测序检测肿瘤细胞DNA微卫星不稳定性(MSI),采用免疫组化法检测肿瘤细胞MMR表达,采用PCR技术检测MMR基因突变情况。结果该家系结直肠癌患者肿瘤组织MSI检测均表现为高度微卫星不稳定性(MSI-H);肿瘤组织MMR家族中MLH1表达均为阴性;MLH1基因第一外显子存在2个新的错义突变位点c.264G>T、c.265G>T,其中c.265G>T突变导致MLH1基因蛋白质翻译在该位点提前终止。结论回族Lynch综合征家系存在MLH1基因突变,即存在第一外显子错义突变位点c.265G>T。

Objective To investigate the expression and mutations of DNA mismatch repair（ MMR） of Lynch syndrome in the members of a Chinese Hui family. Methods The propositus was male,37 years old,the forth generation,Hui nationality,had rectal poorly differentiated adenocarcinoma. There were six generations existing（ Hui nationality）,and a total of 14 patients with colorectal cancer were found including 7 living cases. The peripheral blood and tumor tissue DNA was collected from 6 cases of patients and 5 healthy controls. The microsatellite instability（ MSI） was detected through DNA sequencing,the expression of MMR protein was measured using immunohistochemistry,and MMR gene mutations was detected by PCR amplification. Results The MSI detection of tumor tissues in the family members demonstrated MSI-H. The immunohistochemistry showed that MLH1 protein was negative. Two new missense mutation sites（ c. 264 G〉 T and c. 265 G 〉T） in the first exon of MLH1 gene were found in 6 patients and 1 normal individual,and c. 264 G 〉T mutation led to early termination of MLH1 protein translation on this site. Conclusion There is MLH1 mutation in Hui family with Lynch syndrome,that is the missense muntation site c. 264 G〉 T in the first exon of MLH1 gene.