A Novel Case of Biallelic MLH3 Variants in a Patient With Rectal Cancer and Polyps.

Abstract

An increasing number of autosomal recessive forms of adenomatous polyposis have been described, but some in very few cases. Here, we describe a rare case of biallelic germline pathogenic variants in the MLH3 gene, implicating it as a potential cause of early colorectal cancer. The patient, a 47-year-old woman, presented with rectal bleeding, leading to the discovery of a malignant rectal tumor and adenomas during colonoscopy. Histopathological examination confirmed adenocarcinoma without microsatellite instability, and genetic testing identified two likely pathogenic frameshift variants in MLH3 located in trans. These findings contribute to the expanding knowledge of MLH3-related polyposis and colorectal cancer and underscore the need for further research into the gene's broader implications, including its potential role in cancer and infertility pathways.