title: 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.
authors: Department of Oncology, Institute for Clinical Sciences, Lund University 22185, Lund, Sweden ; The Danish HNPCC-register, Clinical Research Centre, Hvidovre University Hospital, Copenhagen University Hvidovre, Denmark.
authors: Mev
authors: M
authors: Dominguez-Valentin
authors: Department of Toxicogenetics, Leiden University Medical Center Leiden, The Netherlands.
authors: Mark
authors: M
authors: Drost
authors: The Danish HNPCC-register, Clinical Research Centre, Hvidovre University Hospital, Copenhagen University Hvidovre, Denmark.
authors: Christina
authors: C
authors: Therkildsen
authors: Department of Oncology, Institute for Clinical Sciences, Lund University 22185, Lund, Sweden.
authors: Eva
authors: E
authors: Rambech
authors: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University Lund, Sweden.
authors: Hans
authors: H
authors: Ehrencrona
authors: Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen DK-2200, Copenhagen N, Denmark.
authors: Maria
authors: M
authors: Angleys
authors: Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen DK-2200, Copenhagen N, Denmark.
authors: Thomas
authors: T
authors: Lau Hansen
authors: Department of Toxicogenetics, Leiden University Medical Center Leiden, The Netherlands.
authors: Niels
authors: N
authors: de Wind
authors: Department of Oncology, Institute for Clinical Sciences, Lund University 22185, Lund, Sweden ; The Danish HNPCC-register, Clinical Research Centre, Hvidovre University Hospital, Copenhagen University Hvidovre, Denmark.
authors: Mef
authors: M
authors: Nilbert
authors: Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen DK-2200, Copenhagen N, Denmark.
authors: Lene
authors: L
authors: Juel Rasmussen
keywords: Functional assay; Lynch syndrome; MLH1; mismatch repair