EPCAM, an epithelial cell-specific adhesion molecule with no known direct function in DNA repair processes has been implicated to cause LS as its gene is located 17 kb upstream of MSH2. EPCAM 3′ deletions result in ablated EPCAM transcriptional termination, aberrant transcription leading to downstream transcriptional interference and MSH2 promoter DNA hypermethylation resulting in loss of MSH2 expression11. Here, MSH2 is linked to Leigh syndrome.