Novel MSH2 splice-site mutation in a young patient with Lynch syndrome

Liccardo,Raffaella; De Rosa,Marina; Izzo,Paola; Duraturo,Francesca

doi:10.3892/mmr.2018.8752

Novel MSH2 splice-site mutation in a young patient with Lynch syndrome

Authors:
- Raffaella Liccardo
- Marina De Rosa
- Paola Izzo
- Francesca Duraturo
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Affiliations: Department of Molecular Medicine and Medical Biotechnology, University of Naples ‘Federico II’, Naples, Italy
Published online on: March 15, 2018 https://doi.org/10.3892/mmr.2018.8752
Pages: 6942-6946
Copyright: © Liccardo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Lynch Syndrome (LS) is associated with germline mutations in one of the mismatch repair (MMR) genes, including MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6, PMS1 homolog 2, mismatch repair system component (PMS2), MLH3 and MSH3. The mutations identified in MMR genes are point mutations or large rearrangements. The point mutations are certainly pathogenetic whether they determine formation of truncated protein. The mutations that arise in splice sites are classified as ‘likely pathogenic’ variants. In the present study, a novel splicing mutation was identified, (named c.212‑1g>a), in the MSH2 gene. This novel mutation in the consensus splice site of MSH2 exon 2 leads to the loss of the canonical splice site, without skipping in‑frame of exon 2; also with the formation of 2 aberrant transcripts, due to the activation of novel splice sites in exon 2. This mutation was identified in a young patient who developed colon cancer at the age of 26 years and their belongs to family that met the ‘Revised Amsterdam Criteria’. The present study provided insight into the molecular mechanism determining the pathogenicity of this novel MSH2 mutation and it reaffirms the importance of genetic testing in LS.

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