Among these, the accuracy of DNA replication relies on DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2. Germline deficiency in MMR genes (MMRd) leads to Lynch syndrome (LS) via monoallelic mutation or constitutional mismatch repair deficiency syndrome (CMMRD) via biallelic mutation. Here, MLH1 is linked to Leigh syndrome.