Some missense alterations in the DNA binding cleft occur in patients with a personal and family history consistent with the developing disease spectrum for PAPP including several meeting Amsterdam criteria for Lynch Syndrome.
In support of literature findings3, 6, our two internal probands with POLE p.L424V have a primary CNS tumor in addition to polyposis and the one female also has a history of endometrial cancer. CNS tumors may need to be formally added to the disease spectrum for this pathogenic mutation.
A large family, in which 11/23 individuals with known POLD1 genotype carry the p.L474P pathogenic mutation, is segregating the mutation with disease with an LOD score of 3.1 and has an average age at diagnosis of colorectal and endometrial cancer that is respectively higher and lower than what has been observed in the literature3,6.
Authors: Marcy Richardson; Robert Huether; Felicia Hernandez; Shuwei Li; Carin Espenschied; AJ Stuenkel; Tina Pesaran