title: A study on MSH2 and MLH1 mutations in hereditary nonpolyposis colorectal cancer families from the Basque Country, describing four new germline mutations.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) or Lynch syndrome underlies between 2 and 5% of all colorectal cancer. It is inherited as an autosomal dominant condition due to mutations in the mismatch repair genes. Fifty-four non-related index cases, 21 of them fulfilling Amsterdam criteria I or II, were studied. Ten (10/21 = 47.6%) different pathological mutations were found in this group, two of which had not previously been reported--one in MLH1 and the other in MSH2-. In the remaining patients, we also found another family with one of these new mutations, and four additional changes, two of which were also new--a pathological change in MSH2 and a second change of uncertain significance in MLH1-, while the other two changes had already been reported. Of all mutations, eight were found in MSH2 (8/15 = 53.3%) and seven in MLH1 (7/15 = 46.6%), suggesting a slightly greater involvement of MSH2 in HNPCC than MLH1 in our population, in contrast to the results reported by other authors.
authors.affiliation: Laboratorio de Genética Molecular, Servicio de Bioquímica, Hospital de Cruces, 48903 Barakaldo-Bizkaia, Spain. cmbouzas@universia.es
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez-Bouzas
authors.forename: Elena
authors.initials: E
authors.lastname: Beristain
authors.forename: Enrique
authors.initials: E
authors.lastname: Ojembarrena
authors.forename: Jose
authors.initials: J
authors.lastname: Errasti
authors.forename: Karmele
authors.initials: K
authors.lastname: Mujika
authors.forename: Noelia
authors.initials: N
authors.lastname: Viguera
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Tejada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013030:Spain
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein