title: Six novel heterozygous MLH1, MSH2, and MSH6 and one homozygous MLH1 germline mutations in hereditary nonpolyposis colorectal cancer.
abstract: Most hereditary nonpolyposis colorectal cancer (HNPCC) cases are caused by germline mutations of mismatch repair (MMR) genes (i.e., MLH1, MSH2, or MSH6). Here we describe six novel mutations in patients referred for genetic assessment. All of these mutations lead to premature translation termination. Five single base pair deletions lead to frameshift (MLH1: g.38-39insCCCA, g.1971del.T; MSH2: g.163del.C, g.746del.A; MSH6: g.3320del.A) and one nonsense mutation in MSH2 g.1030C>T leads to a stop codon: p.Q344X. In one patient, the previously described MLH1 nonsense mutation g.806C>G was found in a homozygous state. In this patient, the familial histories of both the mother and father suggested HNPCC syndrome. This patient developed colon cancer at 22 years of age, suggesting a more aggressive phenotype. The results of our study provide further insight into the mutational spectrum of MMR genes in HNPCC families.
authors.affiliation: Laboratoire de Biologie Cellulaire et Hormonale, Hôpital Arnaud de Villenueve, Centre Hospitalier Universitaire, Montpellier, cedex France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Rey
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Noruzinia
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Brouillet
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Thierry
authors.initials: T
authors.lastname: Maudelonde
authors.forename: Pascal
authors.initials: P
authors.lastname: Pujol
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D020137:Base Pair Mismatch; D002352:Carrier Proteins; D043171:Chromosomal Instability; D003062:Codon; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D018095:Germ-Line Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003062:Codon; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein