MLH1 and Lynch syndrome: According to the mutant number of microsatellite sites, MMR defects can arise from somatic mutations, epigenetic silencing (such as hypermethylation of the hMLH1 promoter in sporadic cases), or germline genetic alterations (as seen in Lynch syndrome), resulting in MSI due to point mutations in MMR genes like hMSH2, hMSH6, hMLH1, PMS2, and PMS1 [36].