Functional characterization of MLH1 missense variants unveils mechanisms of pathogenicity and clarifies role in cancer.

ABSTRACT: Lynch syndrome is a heritable condition caused by a heterozygous germline inactivating mutation of the DNA mismatch repair (MMR) genes, most commonly the MLH1 gene. However, one third of the identified alterations are missense variants, for which the clinical significance is unclear in many cases. We have identified three MLH1 missense alterations (p.(Glu736Lys), p.(Pro640Thr) and p.(Leu73Pro)) in six individuals from large Tunisian families. For none of these alterations, a classification of pathogenicity was available, consequently diagnosis, predictive testing and targeted surveillance in affected families was impossible. We therefore performed functional laboratory testing using a system testing stability as well as catalytic activity that includes clinically validated reference varian

SUBMITTER: Mahdouani M 

PROVIDER: S-EPMC9714755 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature