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

ABSTRACT: 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.

SUBMITTER: Dominguez-Valentin M

PROVIDER: S-EPMC4113276 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Dominguez-Valentin Mev M Drost Mark M Therkildsen Christina C Rambech Eva E Ehrencrona Hans H Angleys Maria M Lau Hansen Thomas T de Wind Niels N Nilbert Mef M Juel Rasmussen Lene L

Molecular genetics & genomic medicine 20140506 4

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 ...[more]

PMID: 25077178

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