Whereas much is known about the occurrence of germline pathogenic variants in MMR genes in the setting of LS [see case 2, MLH1 (NM_000249.3); Exon 16; c.1745T>C], there is recent evidence that also other cancer susceptibility genes, many of them associated with DNA repair, harbor germline variants in individuals affected by CRCs (51, 52, 56). This evidence concerns the gene MLH1 and Leigh syndrome.