Lynch综合征（LS）是一种常染色体显性遗传疾病，其特征为对各种癌症，主要是结直肠癌（CRC）的易感性。LS是由于DNA错配修复基因即mutL同源物1（MLH1），mutS同源物2（MSH2），mutS同源物6（MSH6）和后减数分离增加2（PMS2）的生殖细胞突变所致。本研究报告了一种新的MLH1基因[NM_000249：外显子1：c.99dup p。（Glu34ArgfsTer4）]在一位34岁男性LS患者中的生殖细胞漂移突变。这种MLH1改变在任何数据库或出版物中均未报告。在检测前列腺病变患者的外周血的Sanger测序的确认下，MLH1基因[NM_000249：外显子1：c.99dup p。（Glu34ArgfsTer4）]的漂移突变得到了证实。同时，Sanger测序结果显示该患者的叔叔是携带者。由于该变异的多个下游生殖细胞漂移突变是致病性的，例如MLH1 M35fs，N38fs和S44fs，因此MLH1 p。（Glu34ArgfsTer4）被预测为也可能是致病性。同时，由于重复的c.99dupA早期引入一个早期终止密码子，导致蛋白质失去功能，MutationTaster软件预测这种MLH1突变p。（Glu34ArgfsTer4）是致病的。本研究可能有助于揭示MLH1的突变谱，导致LS。版权所有©2023 Elsevier Inc.

Lynch syndrome (LS) is an autosomal dominant inherited disorder, characterized by a predisposition to various cancers, mainly colorectal cancer (CRC). LS is caused by germline mutations in DNA mismatch repair genes i.e. mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post-meiotic segregation increased 2 (PMS2). In this study, we report a novel germline frameshift mutation in the MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] in a 34-year-old male patient with LS. This MLH1 alteration has never been reported in any database or any publications. The frameshift mutation in MLH1 gene [NM_000249: exon1: c.99dup p.(Glu34ArgfsTer4)] was confirmed by Sanger sequencing conducted on peripheral blood of the proband. Meanwhile, Sanger sequencing results revealed the proband's uncle was the carrier. As multiple downstream germline frameshift mutations of this variation are pathogenic, such as MLH1 M35fs, N38fs, and S44fs, it is predicted that MLH1 p.(Glu34ArgfsTer4) might be also pathogenic. Meanwhile, this MLH1 mutation p.(Glu34ArgfsTer4) is predicted to be disease-causing by the MutationTaster software, as the duplication c.99dupA introduced a premature stop codon early in the translation, resulting in a non-functional protein. This study may contribute to the mutational spectrum of MLH1 leading to LS.Copyright © 2023. Published by Elsevier Inc.