title: A missense germline mutation in exon 7 of the MSH2 gene in a HNPCC family from center-Italy.
abstract: BACKGROUND
  Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is an autosomal dominant inherited disease predisposing to the development of colorectal cancers and several other malignancies (endometrium, ovaries, stomach, small bowel, hepatobiliary and urinary tract). HNPCC is caused by germline mutations in any of the MisMatch Repair (MMR) genes. Mutations in MLH1 and MSH2 account for almost 90% of all identified ones. About 15% of mutations identified in MSH2 are missense ones.
  
  
  METHODS
  We studied one family, fulfilling Amsterdam II criteria, referred to our Center for genetic counselling. The proband, and some of her relatives, have been investigated for microsatellite instability (MSI), immunohistochemical MMR protein staining and by direct sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA).
  
  
  RESULTS
  All patients carried the same novel MSH2 germline missense mutation (R359S) in exon 7, which determines the substitution of an Arginine, which is a basic amino acid, with a polar Serine residue (R359S). The mutation was associated with lack of expression of MSH2 protein and high microsatellite instability in tumour tissues. The same mutation has been detected in one healthy relative.
  
  
  CONCLUSIONS
  The mutation here reported shows a high correlation with phenotype. The mutation is located in an evolutionary conserved domain. Taken together, our findings suggest evidence that the amino acid substitution can be interpreted as pathogenetic.
authors.affiliation: Istituto di Medicina Clinica e Biotecnologie Applicate-Oncologia Medica, Università Politecnica delle Marche, via Tronto, 60020 Ancona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchi
authors.forename: Eva
authors.initials: E
authors.lastname: Galizia
authors.forename: Emilio
authors.initials: E
authors.lastname: Porfiri
authors.forename: Laura
authors.initials: L
authors.lastname: Belvederesi
authors.forename: Romina
authors.initials: R
authors.lastname: Catalani
authors.forename: Cristian
authors.initials: C
authors.lastname: Loretelli
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bracci
authors.forename: Italo
authors.initials: I
authors.lastname: Bearzi
authors.forename: Chiara
authors.initials: C
authors.lastname: Turchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Viel
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cellerino
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007558:Italy; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D051718:MutS Homolog 2 Protein / Q000172:deficiency / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D010375:Pedigree; D012694:Serine / Q000235:genetics
chemical_list: D015345:Oligonucleotide Probes; D012694:Serine; D001120:Arginine; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein