First report of MUTYH-associated polyposis with c.1353_1355del and c.452A>G mutations in Tolima Grande region from Colombia: a case report.

INTRODUCTION: The MUTYH gene encodes a protein involved in DNA repair and is known for MUTYH-associated polyposis (MAP), a rare autosomal recessive condition that predisposes individuals to colorectal cancer (CRC), colorectal polyps and familial colorectal cancer syndrome. CASE REPORT: We describe the first Tolima Grande region from a Colombian report of individuals carrying pathogenic MUTYH variants c.452A>G and c.1353_1355del associated with polyposis phenotypes. Three main cases with detailed histopathological findings and family history are presented. Additionally, independent findings from Clinaltec identified three further individuals carrying c.452A>G and one heterozygous carrier of c.1353_1355del detected during predictive multigene panel testing. DISCUSSION: These cases highlight the diagnostic and clinical challenges of distinguishing biallelic pathogenic MUTYH variants, which define MAP and confer high CRC risk, from monoallelic carriers, whose cancer risk is substantially lower. Misclassification may result in inappropriate surveillance strategies and missed opportunities for early detection. From a public health perspective, these findings emphasize persistent gaps in hereditary CRC prevention in underrepresented populations, including fragmented cancer registries and limited incorporation of genetic and family history data into clinical decision-making. CONCLUSION: This report provides evidence in Colombia of polyposis-associated pathogenic MUTYH variants c.452A>G and c.1353_1355del, underscoring the importance of expanding genetic evaluation for hereditary CRC in Latin American populations.