title: Novel MLH1 duplication identified in Colombian families with Lynch syndrome.
abstract: OBJECTIVE
  Lynch syndrome accounts for 2-4% of all colorectal cancer, and is mainly caused by germline mutations in the DNA mismatch repair genes. Our aim was to characterize the genetic mutation responsible for Lynch syndrome in an extensive Colombian family and to study its prevalence in Antioquia.
  
  
  METHODS
  A Lynch syndrome family fulfilling Amsterdam criteria II was studied by immunohistochemistry and by multiplex ligation-dependent probe amplification (MLPA). Results were confirmed by additional independent MLPA, Southern blotting, and sequencing.
  
  
  RESULTS
  Index case tumor immunohistochemistry results were MLH1-, MSH2+, MSH6+, and PMS2-. MLPA analysis detected a duplication of exons 12 and 13 of MLH1. This mutation was confirmed and characterized precisely to span 4219 base pairs. Duplication screening in this family led to the identification of six additional carriers and 13 noncarriers. We also screened 123 early-onset independent colorectal cancer cases from the same area and identified an additional unrelated carrier.
  
  
  CONCLUSIONS
  A novel duplication of exons 12 and 13 of the MLH1 gene was detected in two independent Lynch syndrome families from Colombia. A putative founder effect and prescreening Lynch syndrome Antioquia families for this specific mutation before thorough mismatch repair mutational screening could be suggested.
authors.affiliation: Gastroenterology Department, Institut de Malalties Digestives i Metabòliques, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Alonso-Espinaco
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Giráldez
authors.forename: Carlos
authors.initials: C
authors.lastname: Trujillo
authors.forename: Heleen
authors.initials: H
authors.lastname: van der Klift
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.forename: Teresa
authors.initials: T
authors.lastname: Ocaña
authors.forename: Irene
authors.initials: I
authors.lastname: Madrigal
authors.forename: Angela M
authors.initials: AM
authors.lastname: Jones
authors.forename: M Magdalena
authors.initials: MM
authors.lastname: Echeverry
authors.forename: Alejandro
authors.initials: A
authors.lastname: Velez
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Montserrat
authors.initials: M
authors.lastname: Milà
authors.forename: Juul
authors.initials: J
authors.lastname: Wijnen
authors.forename: Luis
authors.initials: L
authors.lastname: Carvajal-Carmona
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000251:Adenosine Triphosphatases / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000235:genetics; D003105:Colombia; D015179:Colorectal Neoplasms / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D020440:Gene Duplication; D018095:Germ-Line Mutation; D006801:Humans; D007150:Immunohistochemistry; D053842:Microsatellite Instability; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; C497172:MSH2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D045643:DNA Repair Enzymes