LS is characterized by the heterozygous germline pathogenic variant in the coding sequence or regulatory domains of the mismatch repair (MMR) genes, most commonly MLH1, MSH2, MSH6, or PMS2. MMR proteins are associated with the detection and correction of DNA replication errors and a compromised MMR system can result in the mutator phenotype and the accumulation of somatic mutations can subsequently lead to carcinogenesis (1). The gene discussed is MSH6; the disease is Leigh syndrome.