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Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation
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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182575/ https://www.ncbi.nlm.nih.gov/pubmed/29288294 http://dx.doi.org/10.1007/s10689-017-0067-x |
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author | von Salomé, Jenny Liu, Tao Keihäs, Markku Morak, Moni Holinski-Feder, Elke Berry, Ian R. Moilanen, Jukka S. Baert-Desurmont, Stéphanie Lindblom, Annika Lagerstedt-Robinson, Kristina |
author_facet | von Salomé, Jenny Liu, Tao Keihäs, Markku Morak, Moni Holinski-Feder, Elke Berry, Ian R. Moilanen, Jukka S. Baert-Desurmont, Stéphanie Lindblom, Annika Lagerstedt-Robinson, Kristina |
author_sort | von Salomé, Jenny |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6182575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-61825752018-10-22 Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation von Salomé, Jenny Liu, Tao Keihäs, Markku Morak, Moni Holinski-Feder, Elke Berry, Ian R. Moilanen, Jukka S. Baert-Desurmont, Stéphanie Lindblom, Annika Lagerstedt-Robinson, Kristina Fam Cancer Original Article 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. Springer Netherlands 2017-12-29 2018 /pmc/articles/PMC6182575/ /pubmed/29288294 http://dx.doi.org/10.1007/s10689-017-0067-x Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), 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. |
spellingShingle | Original Article von Salomé, Jenny Liu, Tao Keihäs, Markku Morak, Moni Holinski-Feder, Elke Berry, Ian R. Moilanen, Jukka S. Baert-Desurmont, Stéphanie Lindblom, Annika Lagerstedt-Robinson, Kristina Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation |
title | Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation |
title_full | Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation |
title_fullStr | Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation |
title_full_unstemmed | Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation |
title_short | Haplotype analysis suggest that the MLH1 c.2059C > T mutation is a Swedish founder mutation |
title_sort | haplotype analysis suggest that the mlh1 c.2059c > t mutation is a swedish founder mutation |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182575/ https://www.ncbi.nlm.nih.gov/pubmed/29288294 http://dx.doi.org/10.1007/s10689-017-0067-x |
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