1. A novel POLD1 pathogenic variant identified in two families with a cancer spectrum mimicking Lynch syndrome
- Author
-
Clémentine Legrand, Marine Lebrun, Pierre Naïbo, Magalie Peysselon, Fabienne Prieur, Caroline Kientz, Françoise Desseigne, Sandrine Handallou, Jean-Marc Rey, Sophie Nambot, Vincent Goussot, Nadim Hamzaoui, and Qing Wang
- Subjects
Adult ,Aged, 80 and over ,Male ,Heterozygote ,Colonic Polyps ,General Medicine ,Middle Aged ,Colorectal Neoplasms, Hereditary Nonpolyposis ,Pedigree ,Diagnosis, Differential ,Phenotype ,Mutation ,Genetics ,Humans ,Female ,Genetics (clinical) ,Aged ,DNA Polymerase III - Abstract
The POLD1 gene is involved in DNA proofreading to ensure accurate DNA replication. Some germline alterations in its exonuclease domain are associated with predisposition to cancers and colonic polyps. Only a few pathogenic variants have been clearly identified so far. Here we report a novel variant: c.1458GT p.(Lys486Asn) that we classified as pathogenic, detected in two putatively unrelated families. The cancer spectrum was very similar to Lynch syndrome, implying an overlapped tissue susceptibility. The common presence of colonic polyps in carriers and the MMR proficient phenotype in tumors were distinctive features suggesting POLD1 implication. Some clinical characteristics observed in the carriers of this variant differed from those reported previously, suggesting a potential genotype/phenotype correlation, and very likely in relation to the functional importance of affected residues. Our findings provide further insight into understanding the role of POLD1 in cancer-related risk.
- Published
- 2022
- Full Text
- View/download PDF