Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein

In clinical genetic diagnostics, it is difficult to predict whether genetic mutations that do not greatly alter the primary sequence of the encoded protein causing unknown functional effects on cognate proteins lead to development of disease. Here, we report the clinical identification of c.2038 T&g...

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Autores principales: Dominguez-Valentin, Mev, Drost, Mark, Therkildsen, Christina, Rambech, Eva, Ehrencrona, Hans, Angleys, Maria, Lau Hansen, Thomas, de Wind, Niels, Nilbert, Mef, Juel Rasmussen, Lene
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BlackWell Publishing Ltd 2014
Materias:
Brief Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113276/
https://www.ncbi.nlm.nih.gov/pubmed/25077178
http://dx.doi.org/10.1002/mgg3.80
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author Dominguez-Valentin, Mev
Drost, Mark
Therkildsen, Christina
Rambech, Eva
Ehrencrona, Hans
Angleys, Maria
Lau Hansen, Thomas
de Wind, Niels
Nilbert, Mef
Juel Rasmussen, Lene
author_facet Dominguez-Valentin, Mev
Drost, Mark
Therkildsen, Christina
Rambech, Eva
Ehrencrona, Hans
Angleys, Maria
Lau Hansen, Thomas
de Wind, Niels
Nilbert, Mef
Juel Rasmussen, Lene
author_sort Dominguez-Valentin, Mev
collection PubMed
description In clinical genetic diagnostics, it is difficult to predict whether genetic mutations that do not greatly alter the primary sequence of the encoded protein causing unknown functional effects on cognate proteins lead to development of disease. Here, we report the clinical identification of c.2038 T>C missense mutation in exon 18 of the human MLH1 gene and biochemically characterization of the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch repair and, therefore, contributing to LS in the carriers.
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spelling pubmed-41132762014-07-30 Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein Dominguez-Valentin, Mev Drost, Mark Therkildsen, Christina Rambech, Eva Ehrencrona, Hans Angleys, Maria Lau Hansen, Thomas de Wind, Niels Nilbert, Mef Juel Rasmussen, Lene Mol Genet Genomic Med Brief Report In clinical genetic diagnostics, it is difficult to predict whether genetic mutations that do not greatly alter the primary sequence of the encoded protein causing unknown functional effects on cognate proteins lead to development of disease. Here, we report the clinical identification of c.2038 T>C missense mutation in exon 18 of the human MLH1 gene and biochemically characterization of the p.Cys680Arg mutant MLH1 protein to implicate it in the pathogenicity of the Lynch syndrome (LS). We show that the mutation is deficient in DNA mismatch repair and, therefore, contributing to LS in the carriers. BlackWell Publishing Ltd 2014-07 2014-05-06 /pmc/articles/PMC4113276/ /pubmed/25077178 http://dx.doi.org/10.1002/mgg3.80 Text en © 2014 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Brief Report
Dominguez-Valentin, Mev
Drost, Mark
Therkildsen, Christina
Rambech, Eva
Ehrencrona, Hans
Angleys, Maria
Lau Hansen, Thomas
de Wind, Niels
Nilbert, Mef
Juel Rasmussen, Lene
Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein
title Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein
title_full Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein
title_fullStr Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein
title_full_unstemmed Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein
title_short Functional implications of the p.Cys680Arg mutation in the MLH1 mismatch repair protein
title_sort functional implications of the p.cys680arg mutation in the mlh1 mismatch repair protein
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113276/
https://www.ncbi.nlm.nih.gov/pubmed/25077178
http://dx.doi.org/10.1002/mgg3.80
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