title: Mismatch repair genes founder mutations and cancer susceptibility in Lynch syndrome.
abstract: Founder mutations in specific populations are common in several Mendelian disorders. They are shared by apparently unrelated families that inherited them from a common ancestor that existed hundreds to thousands of years ago. They have been proven to impact in molecular diagnostics strategies in specific populations, where they can be assessed as the first screening step and, if positive, avoid further expensive gene scanning. In Lynch syndrome (LS), a dominantly inherited colorectal cancer disease, more than 50 founder pathogenic mutations have been described so far in the mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2). We here provide a comprehensive summary of the founder mutations found in the MMR genes and an overview of their main characteristics. At a time when high-throughput strategies are being introduced in the molecular diagnostics of cancer, genetic testing for founder mutations can complement next generation sequencing (NGS) technologies to most efficiently identify MMR gene mutations in any given population. Additionally, special attention is paid to MMR founder mutations with interesting anthropological significance.
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Ponti
authors.forename: E
authors.initials: E
authors.lastname: Castellsagué
authors.forename: C
authors.initials: C
authors.lastname: Ruini
authors.forename: A
authors.initials: A
authors.lastname: Percesepe
authors.forename: A
authors.initials: A
authors.lastname: Tomasi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D019468:Disease Management; D044127:Epigenesis, Genetic; D000071858:Epithelial Cell Adhesion Molecule; D018703:Founder Effect; D005828:Genetics, Population; D018095:Germ-Line Mutation; D006801:Humans; D007585:Jews / Q000235:genetics; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D011159:Population Surveillance; D011379:Prognosis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: HNPCC; Lynch syndrome; MLH1; MMR; MSH2; MSH6; Muir-Torre syndrome; PMS2; founder mutation; genetic anticipation phenomenon