University of Oulu

von Salomé, J., Liu, T., Keihäs, M. et al. Familial Cancer (2018) 17: 531.

Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation

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Author: von Salomé, Jenny1; Liu, Tao2; Keihäs, Markku2;
Organizations: 1Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital
2Department of Molecular Medicine and Surgery, Karolinska Institutet
3Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München
4MGZ – Medizinisch Genetisches Zentrum
5Leeds Genetics Laboratory
6PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu
7Department of Clinical Genetics, Oulu University Hospital
8Department of Genetics, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Inserm U1079, IRIB, University of Rouen, Normandy University
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.9 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2018-10-24


Lynch syndrome (LS) predisposes to a spectrum of cancers and increases the lifetime risk of developing colorectal- or endometrial cancer to over 50%. Lynch syndrome is dominantly inherited and is caused by defects in DNA mismatch-repair genes MLH1, MSH2, MSH6 or PMS2, with the vast majority detected in MLH1 and MSH2. Recurrent LS-associated variants observed in apparently unrelated individuals, have either arisen de novo in different families due to mutation hotspots, or are inherited from a founder (a common ancestor) that lived several generations back. There are variants that recur in some populations while also acting as founders in other ethnic groups. Testing for founder mutations can facilitate molecular diagnosis of Lynch Syndrome more efficiently and more cost effective than screening for all possible mutations. Here we report a study of the missense mutation MLH1 c.2059C > T (p.Arg687Trp), a potential founder mutation identified in eight Swedish families and one Finnish family with Swedish ancestors. Haplotype analysis confirmed that the Finnish and Swedish families shared a haplotype of between 0.9 and 2.8 Mb. While MLH1 c.2059C > T exists worldwide, the Swedish haplotype was not found among mutation carriers from Germany or France, which indicates a common founder in the Swedish population. The geographic distribution of MLH1 c.2059C > T in Sweden suggests a single, ancient mutational event in the northern part of Sweden.

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Series: Familial cancer
ISSN: 1389-9600
ISSN-E: 1573-7292
ISSN-L: 1389-9600
Volume: 17
Issue: 4
Pages: 531 - 537
DOI: 10.1007/s10689-017-0067-x
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3111 Biomedicine
Copyright information: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.