title: AXIN2-associated autosomal dominant ectodermal dysplasia and neoplastic syndrome.
abstract: We describe a family with a novel, inherited AXIN2 mutation (c.1989G>A) segregating in an autosomal dominant pattern with oligodontia and variable other findings including colonic polyposis, gastric polyps, a mild ectodermal dysplasia phenotype with sparse hair and eyebrows, and early onset colorectal and breast cancers. This novel mutation predicts p.Trp663X, which is a truncated protein that is missing the last three exons, including the DIX (Disheveled and AXIN interacting) domain. This nonsense mutation is predicted to destroy the inhibitory action of AXIN2 on WNT signaling. Previous authors have described an unrelated family with autosomal dominant oligodontia and a variable colorectal phenotype segregating with a nonsense mutation of AXIN2, as well as a frameshift AXIN2 mutation in an unrelated individual with oligodontia. Our report provides additional evidence supporting an autosomal dominant AXIN2-associated ectodermal dysplasia and neoplastic syndrome.
authors.affiliation: Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA. monicama@umich.edu
authors.forename: Monica L
authors.initials: ML
authors.lastname: Marvin
authors.forename: Serina M
authors.initials: SM
authors.lastname: Mazzoni
authors.forename: Casey M
authors.initials: CM
authors.lastname: Herron
authors.forename: Sean
authors.initials: S
authors.lastname: Edwards
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Petty
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D060466:Axin Protein; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype
chemical_list: C491761:AXIN2 protein, human; D060466:Axin Protein; D003598:Cytoskeletal Proteins