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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.
Afiliação
  • von Salomé J; Department of Molecular Medicine and Surgery, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Solna, Stockholm, Sweden.
  • Liu T; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Keihäs M; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Morak M; Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
  • Holinski-Feder E; MGZ - Medizinisch Genetisches Zentrum, Munich, Germany.
  • Berry IR; Medizinische Klinik und Poliklinik IV, Campus Innenstadt, Klinikum der Universität München, Munich, Germany.
  • Moilanen JS; MGZ - Medizinisch Genetisches Zentrum, Munich, Germany.
  • Baert-Desurmont S; Leeds Genetics Laboratory, St James's University Hospital, Leeds, UK.
  • Lindblom A; PEDEGO Research Unit and Medical Research Center Oulu, University of Oulu, Oulu, Finland.
  • Lagerstedt-Robinson K; Department of Clinical Genetics, Oulu University Hospital, Oulu, Finland.
Fam Cancer ; 17(4): 531-537, 2018 10.
Article em En | MEDLINE | ID: mdl-29288294
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Haplótipos / Neoplasias Colorretais Hereditárias sem Polipose / Mutação de Sentido Incorreto / Proteína 1 Homóloga a MutL Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Haplótipos / Neoplasias Colorretais Hereditárias sem Polipose / Mutação de Sentido Incorreto / Proteína 1 Homóloga a MutL Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Ano de publicação: 2018 Tipo de documento: Article