title: Double frameshift mutations in APC and MSH2 in the same individual.
abstract: Heterozygous germline DNA mismatch repair gene mutations are typically associated with HNPCC. Here we report the case of a proband whose father was known for familial adenomatous polyposis. The number of polyps (less than ten) was not typical of polyposis; therefore, the diagnosis of HNPCC was entertained. Microsatellite instability analyses were performed on peripheral blood and biopsy of a right-sided dysplastic adenoma. The tumour tissue showed high-grade instability, and subsequently, immunohistochemistry showed that neither MSH2 nor MSH6 proteins were expressed in tumour cells. Prophylactic colectomy was performed, and an adenocarcinoma developing within the adenoma was diagnosed (pT1N0). Genomic DNA analysis revealed a novel mutation in MSH2 as a frameshift mutation in exon 7 (c.1,191_1,192dupG). Both parents of the proband were analyzed for MSH2 and APC mutations, and in the father, a truncating mutation in exon 15 of APC was identified as del3471-3473GAGA. This mutation was found to be present in the proband. His mother was found to bear the MSH2 exon 7 mutation. At follow-up, the proband was diagnosed with fundic, antral and duodenal adenomas (one fundic adenoma showed low-grade dysplasia). Several tubular rectal adenomas with low-grade dysplasia were excised. The patient later developed an intra-abdominal desmoid tumour.
authors.affiliation: Clinic of Visceral Surgery, Geneva University Hospital, Geneva, Switzerland. csoravia@hin.ch
authors.forename: Claudio
authors.initials: C
authors.lastname: Soravia
authors.forename: Celia D
authors.initials: CD
authors.lastname: DeLozier
authors.forename: Zurana
authors.initials: Z
authors.lastname: Dobbie
authors.forename: Claudine Rey
authors.initials: CR
authors.lastname: Berthod
authors.forename: Eviano
authors.initials: E
authors.lastname: Arrigoni
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Bründler
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Pierre
authors.initials: P
authors.lastname: Hutter
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D000328:Adult; D003082:Colectomy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D003937:Diagnosis, Differential; D016368:Frameshift Mutation; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D051718:MutS Homolog 2 Protein / Q000235:genetics*; D010375:Pedigree
chemical_list: C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein