Premium
Inactivation of DNA Mismatch Repair by Variants of Uncertain Significance in the PMS 2 Gene
Author(s) -
Drost Mark,
Koppejan Hester,
Wind Niels
Publication year - 2013
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22426
Subject(s) - pms2 , biology , lynch syndrome , genetics , dna mismatch repair , gene , mutation , dna repair , cancer research
Lynch syndrome ( LS ) is a common cancer predisposition caused by an inactivating mutation in one of four DNA mismatch repair ( MMR ) genes. Frequently a variant of uncertain significance ( VUS ), rather than an obviously pathogenic mutation, is identified in one of these genes. The inability to define pathogenicity of such variants precludes targeted healthcare. Here, we have modified a cell‐free assay to test VUS in the MMR gene PMS 2 for functional activity. We have analyzed nearly all VUS in PMS 2 found thus far and describe loss of MMR activity for five, suggesting the applicability of the assay for diagnosis of LS .