Germline pathogenic variants in HIC1 DNA binding domains are associated with familial serrated polyposis syndrome.

ABSTRACT: Serrated polyposis syndrome (SPS) is characterized by multiple and/or large serrated polyps and increased colorectal cancer (CRC) risk. Germline predisposition to SPS is mostly undetermined. We aimed to identify a new inherited SPS predisposition component by functionally evaluating a candidate gene replicated in two independent SPS cohorts. Exome sequencing was performed in a discovery cohort of 39 patients from 16 SPS families, and validation of relevant results was performed by multi-gene panel sequencing in 211 independent SPS patients. Considering the discovery and validation cohorts, three predicted pathogenic missense variants were identified in HIC1 (Hypermethylated in cancer 1): c.110C>T (p.Ala37Val), c.1295A>G (p.Gln432Arg), and c.1411G>A (p.Gly471Arg). HIC1 is a tumor suppressor

SUBMITTER: Dominguez-Rovira X 

PROVIDER: S-EPMC12280854 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature