Functional and phenotypic consequences of an unusual inversion in MSH2.
Fam Cancer
; 23(1): 1-7, 2024 Mar.
Article
in En
| MEDLINE
| ID: mdl-37957483
ABSTRACT
Lynch syndrome is an autosomal dominant disorder that usually results from a pathogenic germline variant in one of four genes (MSH2, MSH6, MLH1, PMS2) involved in DNA mismatch repair. Carriers of such variants are at risk of developing numerous cancers during adulthood. Here we report on a family suspected of having Lynch syndrome due to a history of endometrial adenocarcinoma, ovarian clear cell carcinoma, and adenocarcinoma of the duodenum in whom we identified a germline 29 nucleotide in-frame inversion in exon 3 of MSH2. We further show that this variant is almost completely absent at the protein level, and that the associated cancers have complete loss of MSH2 and MSH6 expression by immunohistochemistry. Functional investigation of this inversion in a laboratory setting revealed a resultant abnormal protein function. Thus, we have identified an unusual, small germline inversion in a mismatch repair gene that does not lead to a premature stop codon yet appears likely to be causal for the observed cancers.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenocarcinoma
/
Colorectal Neoplasms, Hereditary Nonpolyposis
Limits:
Adult
/
Humans
Language:
En
Journal:
Fam Cancer
Journal subject:
NEOPLASIAS
Year:
2024
Document type:
Article
Affiliation country:
Canadá