LS is caused by heterozygous germline mutations in one of the four key MMR genes, MLH1, MSH2, MSH6, and PMS2. Although more than 1500 variants of mutations have been identified in LS, mutations in MLH1 (40–50%) or MSH2 (34–39%) are the main cause, while those in MSH6 (7–18%) and PMS2 (8%) are rare [10, 17]. Here, MSH2 is linked to Leigh syndrome.