Genotype-phenotype correlations in carriers of the PMS2 founder variant c.1831dup.

ABSTRACT:

Background

Lynch syndrome represents one of the most common cancer predispositions worldwide and is caused by germline pathogenic variants (PV) in DNA mismatch repair (MMR) genes. We repeatedly identified a PV in the MMR gene PMS2, c.1831dup, accounting for 27% of all Swiss PMS2 PV index patients identified. Notably, 2/18 index patients had been diagnosed with colorectal cancer (CRC) before age 30.

Methods

In this study, we investigated if this PV could (i) represent a founder variant by haplotype analysis and (ii) be associated with a more severe clinical phenotype.

Results

Haplotype analysis identified a shared common region of about 0.7 Mb/1.3 cM in 13 (81%) out of 16 index patients. Genotype-phenotype correlations, combining data from the 18 Swiss and 18 literatur

SUBMITTER: Gass M 

PROVIDER: S-EPMC10797823 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature