A frameshift mutation in exon 19 of MLH1 in a Chinese Lynch syndrome family: a pedigree study  

一个中国Lynch综合征家系携带的MLH1基因第19号外显子移码突变:一项家系研究（英文）

作　　者：Qiao-qi SUI Wu JIANG Xiao-dan WU Yi-hong LING Zhi-zhong PAN Pei-rong DING 

机构地区：[1]Department of Colorectal Surgery, Sun Yat-sen University Cancer Center [2]State Key Laboratory of Oncology in South China [3]Department of Pathology, Sun Yat-sen University Cancer Center

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2019年第1期105-108,共4页浙江大学学报（英文版）B辑（生物医学与生物技术）

摘　　要：Lynch syndrome (LS),an autosomal dominantly inherited disease previously known as hereditary non-polyposis coloreetal cancer (HNPCC),leads to a high risk of colorectal cancer (CRC)as well as malignancy at certain sites including endometrium,ovary,stomach,and small bowel (Hampel et al.,2008;Lynch et al.,2009).Clinically,LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005).LS is associated with mutations of DNA mismatch repair (MMR)genes such as MLH1,MSH2, MSH6,PMS2,and EPCAM (Ligtenberg et al.,2009;Lynch et al.,2009),which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes.目的:寻找一个Lynch综合征患者所在家系携带的DNA错配修复基因突变,探讨各突变对肿瘤发生发展的影响。创新点:MLH1的第19号外显子c.2250_2251insAA移码突变既往被认为是意义未名突变,而我们的研究为明确该突变的致病意义提供了依据。另外,我们首次报道了MLH3基因第1号外显子c.1397C>A突变。该突变有可能使Lynch综合征患者的发病年龄提前。方法:运用免疫组织化学技术检测家系先证者肿瘤组织中错配修复基因蛋白的缺失情况,使用二代测序技术通过先证者血标本明确患者所携带的突变。同时运用Sanger法检测家系其他成员该突变的携带情况以明确突变对肿瘤发生发展的影响。结论:我们在患者体内发现MLH1基因第19号外显子移码突变(c.2250_2251insAA)以及MLH3基因第1号外显子c.1397C>A突变。在患者家系中,我们仅检测到有MLH1突变,因此该突变极有可能为致病突变。

关 键 词：Lync综合征 家系 DNA错配修复基因 置换 移码突变 

分 类 号：R596.1[医药卫生—内科学]