title: Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma.
abstract: Autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma is characterized by the adoption of a white, spongy appearance of affected areas upon exposure to water. After exome sequencing, missense mutations were identified in AQP5, encoding water-channel protein aquaporin-5 (AQP5). Protein-structure analysis indicates that these AQP5 variants have the potential to elicit an effect on normal channel regulation. Immunofluorescence data reveal the presence of AQP5 at the plasma membrane in the stratum granulosum of both normal and affected palmar epidermis, indicating that the altered AQP5 proteins are trafficked in the normal manner. We demonstrate here a role for AQP5 in the palmoplantar epidermis and propose that the altered AQP5 proteins retain the ability to form open channels in the cell membrane and conduct water.
authors.affiliation: Centre for Cutaneous Research, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, London E1 2AT, UK. Electronic address: d.blaydon@qmul.ac.uk.
authors.forename: Diana C
authors.initials: DC
authors.lastname: Blaydon
authors.forename: Lisbet K
authors.initials: LK
authors.lastname: Lind
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Linton
authors.forename: Francis J D
authors.initials: FJ
authors.lastname: Smith
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Wilson
authors.forename: W H Irwin
authors.initials: WH
authors.lastname: McLean
authors.forename: Colin S
authors.initials: CS
authors.lastname: Munro
authors.forename: Andrew P
authors.initials: AP
authors.lastname: South
authors.forename: Irene M
authors.initials: IM
authors.lastname: Leigh
authors.forename: Edel A
authors.initials: EA
authors.lastname: O'Toole
authors.forename: Anita
authors.initials: A
authors.lastname: Lundström
authors.forename: David P
authors.initials: DP
authors.lastname: Kelsell
mesh_terms: D051402:Aquaporin 5 / Q000235:genetics*; D001483:Base Sequence; D002462:Cell Membrane / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism* / Q000503:physiopathology; D005799:Genes, Dominant; D006801:Humans; D015776:Keratoderma, Palmoplantar, Diffuse / Q000235:genetics* / Q000503:physiopathology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D021381:Protein Transport; D014867:Water / Q000378:metabolism; D014953:Wrist / Q000503:physiopathology*
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; D014867:Water