MSH2 and Leigh syndrome: LS (formerly known as hereditary nonpolyposis colorectal cancer; HNPCC) is caused by germline pathogenic variants in MLH1, MSH2, MSH6, PMS2 or by deletion of the 3’ end of EPCAM (TACSTD1), resulting in hypermethylation of the MSH2 promoter (Ligtenberg et al., 2009), each of which results in different risks for cancer, particularly CRC, EC, and ovarian cancer.