Lynch syndrome (LS), the single most common inherited cause of CRC, shows an autosomal dominant pattern of inheritance due to germline mutations in either of the genes MLH1, MSH2, MSH6, PMS2, or EPCAM which eventually results in the disruption of DNA mismatch repair (MMR) in LS tumor cells (for reviews, see Kohlmann and Gruber 2004, Lynch et al. 2015). Here, PMS2 is linked to Leigh syndrome.