Insertion of an Alu-like element in MLH1 intron 7 as a novel cause of Lynch syndrome.

ABSTRACT:

Background

Lynch Syndrome (LS) is caused by germline mutations in the DNA mismatch repair (MMR) genes with mutations in MLH1 accounting for ~40% of LS-related alterations.

Methods

MSK-IMPACT analysis was performed on peripheral blood from a patient with early- onset colorectal cancer. Subsequently PCR and sequencing was performed to characterize the insertion. Immunohistochemistry for MMR genes and MLH1 promoter methylation were analyzed on patient's tumor.

Results

MSK-IMPACT germline testing revealed an insertion into c.588+8_588+9 of MLH1 intron 7. The insertion was further characterized as an AluSx-like element with ~115 bp in length. Functional studies demonstrated that the AluSx-like element led to complete disruption of mRNA splicing and probably resulted in tra

SUBMITTER: Li Y 

PROVIDER: S-EPMC7767547 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature