A novel POLD1 pathogenic variant identified in two families with a cancer spectrum mimicking lynch syndrome.

Fiche publication

Date publication

décembre 2021


European journal of medical genetics


Membres identifiés du Cancéropôle Est :
Dr NAMBOT Sophie

Tous les auteurs :
Legrand C, Lebrun M, Naibo P, Peysselon M, Prieur F, Kientz C, Desseigne F, Handallou S, Rey JM, Nambot S, Goussot V, Hamzaoui N, Wang Q


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.1458G > T 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.

Mots clés

Cancer predisposition, Hereditary colorectal cancer, Lynch syndrome, POLD1 gene, PPAP syndrome


Eur J Med Genet. 2021 Dec 22;:104409