Traditionally, the propensity of LS families for CRC or other cancers can be attributed to the presence of pathogenic mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2, or PMS1) or a germline deletion in EPCAM that eventually results in the epigenetic silencing of the MSH2 gene [4, 5]. Here, PMS1 is linked to colorectal carcinoma.