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. The gene discussed is MSH2; the disease is Leigh syndrome.