Novel Mutations inMLH1andMSH2Genes in Mexican Patients with Lynch Syndrome

Abstract

Background. Lynch Syndrome (LS) is characterized by germline mutations in the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2. This syndrome is inherited in an autosomal dominant pattern and is characterized by early onset colorectal cancer (CRC) and extracolonic tumors. The aim of this study was to identify mutations in MMR genes in three Mexican patients with LS. Methods. Immunohistochemical analysis was performed as a prescreening method to identify absent protein expression. PCR, Denaturing High Performance Liquid Chromatography (dHPLC), and Sanger sequencing complemented the analysis. Results. Two samples showed the absence of nuclear staining for MLH1 and one sample showed loss of nuclear staining for MSH2. The mutations found in MLH1 gene were c.2103+1G>C in intron 18 and compound heterozygous mutants c.1852_1854delAAG (p.K618del) and c.1852_1853delinsGC (p.K618A) in exon 16. In the MSH2 gene, we identified mutation c.638dupT (p.L213fs) in exon 3. Conclusions. This is the first report of mutations in MMR genes in Mexican patients with LS and these appear to be novel.

Lynch syndrome in Mexican-Mestizo families: Genotype, phenotypes, and challenges in cascade testing among relatives at risk

“…Only eight studies have reported data on Mexican-Mestizo patients with molecularly confirmed LS [ 5 , 8 , [20] , [21] , [22] , [23] , [24] , [25] ] shown in Table 4 . In the present study, the MLH1 gene (67.5 %) was more frequently affected than MSH2 (22.5 %).…”

Genomic instability and the link to infertility: A focus on microsatellites and genomic instability syndromes

“…Lynch syndrome (LS) (OMIM #120435) is associated with variants in MLH1 [137],MSH2 [138],MSH6 [68], and/or PMS2 [139]. These variants contribute to the onset of multiple cancers including endometrial [96], breast [140], colorectal [141], and prostate [142].…”

Evaluation of genetic alterations in hereditary cancer susceptibility genes in the Ashkenazi Jewish women community of Mexico

“…While various studies have identified germline pathogenic variants associated with hereditary cancer syndromes in the Mexican population, there is currently no information on genetic alterations specifically focused on Mexicans who self-identify as AJ (Torres-Mejía et al, 2015;Villarreal-Garza et al, 2015;Moreno-Ortiz et al, 2016;Quezada Urban et al, 2018;Gallardo-Rincón et al, 2020). The lack of this information remains an important limitation to further evaluate the implications of identifying high risk populations in genomic testing and public health policies in Mexico.…”