| First Author | Wielders E | Year | 2017 |
| Journal | Fam Cancer | Volume | 16 |
| Issue | 2 | Pages | 221-229 |
| PubMed ID | 27873144 | Mgi Jnum | J:320945 |
| Mgi Id | MGI:6882960 | Doi | 10.1007/s10689-016-9945-x |
| Citation | Wielders E, et al. (2017) Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch repair and is causative for Lynch syndrome. Fam Cancer 16(2):221-229 |
| abstractText | Missense variants of DNA mismatch repair (MMR) genes pose a problem in clinical genetics as long as they cannot unambiguously be assigned as the cause of Lynch syndrome (LS). To study such variants of uncertain clinical significance, we have developed a functional assay based on direct measurement of MMR activity in mouse embryonic stem cells expressing mutant protein from the endogenous alleles. We have applied this protocol to a specific truncation mutant of MSH2 that removes 60 C-terminal amino acids and has been found in suspected LS families. We show that the stability of the MSH2/MSH6 heterodimer is severely perturbed, causing attenuated MMR in in vitro assays and cancer predisposition in mice. This mutation can therefore unambiguously be considered as deleterious and causative for LS. |
