Functional studies of a novel Germline p53 splicing mutation identified in a patient with Li–Fraumeni‐Like syndrome

Most p53 mutations identified in Li–Fraumeni syndrome (LFS) are missense mutations; splicing mutations have rarely been reported. A novel splicing p53 mutation was identified in a patient with Li–Fraumeni‐like syndrome (LFL). Usually, p53 missense mutants identified in LFS and cancer cells function as dominant negative mutations interfering with wild‐type p53 function. However, the mechanism by which p53 haploinsufficiency causes carcinogenesis is not well characterized. In this study, we describe a novel splicing mutation that results in the loss‐of‐function of p53. These findings suggest a linkage between the loss‐of‐function type p53 mutation and a LFL phenotype. © 2012 Wiley Periodicals, Inc.