title: First description of mutational analysis of MLH1, MSH2 and MSH6 in Algerian families with suspected Lynch syndrome.
abstract: Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer (CRC) linked to germline defects in Mismatch Repair (MMR) genes. We present here, the first molecular study of the correlation between CRC and mutations occurring in these genes performed in twenty-one unrelated Algerian families. The presence of germline mutations in MMR genes, MLH1, MSH2 and MSH6 genes was tested by sequencing all exons plus adjacent intronic sequences and Multiplex ligand-dependent probe amplification (MLPA) for testing large genomic rearrangements. Pathogenic mutations were identified in 20 % of families with clinical suspicion on HNPCC. Two novel variants described for the first time in Algerian families were identified in MLH1, c.881_884delTCAGinsCATTCCT and a large deletion in MSH6 gene from a young onset of CRC. Moreover, the variants of MSH2 gene: c.942+3A>T, c.1030C>T, the most described ones, were also detected in Algerian families. Furthermore, the families HNPCC caused by MSH6 germline mutation may show an age of onset that is comparable to this of patients with MLH1 and MSH2 mutations. In this study, we confirmed that MSH2, MLH1, and MSH6 contribute to CRC susceptibility. This work represents the implementation of a diagnostic algorithm for the identification of Lynch syndrome patients in Algerian families.
authors.affiliation: Department of Animal Biology, Faculty of Natural and Life Science, University 1, Mentouri Brothers, Constantine, Algeria. zhadia@gmail.com.|Laboratory of Biology and Molecular Genetics, Faculty of Medicine, University 3, Rabah Bitat, Constantine, Algeria. zhadia@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Ziada-Bouchaar
authors.affiliation: Laboratory of Biology and Molecular Genetics, Faculty of Medicine, University 3, Rabah Bitat, Constantine, Algeria.
authors.forename: K
authors.initials: K
authors.lastname: Sifi
authors.affiliation: Laboratory of Biology and Molecular Genetics, Faculty of Medicine, University 3, Rabah Bitat, Constantine, Algeria.|Medical Oncology Service, University Hospital Center, Benbadis, Constantine, Algeria.
authors.forename: T
authors.initials: T
authors.lastname: Filali
authors.affiliation: Laboratory of Biology and Molecular Genetics, Faculty of Medicine, University 3, Rabah Bitat, Constantine, Algeria.|Gastroenterology Service, University Hospital Center, Benbadis, Constantine, Algeria.
authors.forename: T
authors.initials: T
authors.lastname: Hammada
authors.affiliation: Department of Animal Biology, Faculty of Natural and Life Science, University 1, Mentouri Brothers, Constantine, Algeria.|Laboratory of Biology and Molecular Genetics, Faculty of Medicine, University 3, Rabah Bitat, Constantine, Algeria.
authors.forename: D
authors.initials: D
authors.lastname: Satta
authors.affiliation: Laboratory of Biology and Molecular Genetics, Faculty of Medicine, University 3, Rabah Bitat, Constantine, Algeria.
authors.forename: N
authors.initials: N
authors.lastname: Abadi
mesh_terms: D000328:Adult; D000462:Algeria; D015179:Colorectal Neoplasms / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics*; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D009154:Mutation; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; C094443:G-T mismatch-binding protein; C501486:MLH1 protein, human; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein
keywords: Algerian families; Hereditary non-polyposis colorectal cancer; Lynch syndrome; MLH1; MMR genes