While it is not associated with Lynch syndrome, at least one case of CRMMD attributed to biallelic PMS1 germline mutation49, somatic loss of the wild-type allele in an individual with a germline deletion of PMS1 and multiple tumor types50, and reduced PMS1 in oral squamous cell carcinoma without PMS1 mutation all point to the need to better understand the potential consequences of life-long downregulation of PMS1 which could also have effects beyond DNA repair51. This evidence concerns the gene PMS1 and Lynch syndrome.