title: A novel AXIN2 germline variant associated with attenuated FAP without signs of oligondontia or ectodermal dysplasia.
abstract: Truncating mutations in the AXIN2 gene, a key regulator of β-catenin degradation in the Wnt pathway, have been reported in three families with gastrointestinal adenomatous polyposis and features of ectodermal dysplasia. However, the role of AXIN2 in familial adenomatous polyposis (FAP) syndrome is not completely understood. We performed an in-depth study of APC and MUTYH, and ruled out their implication in 23 FAP families. We then investigated the role of other genes involved in the Wnt pathway, including AXIN2, and identified a novel missense variant in AXIN2 in one family with attenuated FAP. Carriers of the variant exhibited a variable number of polyps but none showed any sign of ectodermal dysplasia. We have demonstrated the pathogenicity of this novel variant by establishing its low frequency in controls as well as by LOH analysis, a segregation study, and immunofluorescent staining of AXIN2 and β-catenin proteins. This report expands the phenotype known to be related to AXIN2 alterations and raises the question of whether to screen AXIN2 in FAP cases negative for alterations in APC and MUTYH.
authors.affiliation: Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Rivera
authors.affiliation: General Surgery Service, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Perea
authors.affiliation: Gastro-Endoscope Service, Clínica Ntra. Sra. Del Rosario, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Sánchez
authors.affiliation: Gastro-Endoscope Service, Clínica Ntra. Sra. Del Rosario, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Villapún
authors.affiliation: Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Sánchez-Tomé
authors.affiliation: Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Mercadillo
authors.affiliation: 1] Hereditary Endocrine Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain [2] Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Robledo
authors.affiliation: 1] Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain [2] Human Genetics Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Benítez
authors.affiliation: 1] Familial Cancer Clinical Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain [2] Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Urioste
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060466:Axin Protein / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D018095:Germ-Line Mutation; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D014071:Tooth Abnormalities / Q000175:diagnosis / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C555337:APC protein, human; C491761:AXIN2 protein, human; D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; D051176:beta Catenin; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase