title: Knuckle pads, in an epidermal palmoplantar keratoderma patient with Keratin 9 R163W transgrediens expression.
abstract: Epidermolytic PalmoPlantar keratoderma (EPPK) Vörner-type is an autosomal dominantly inherited skin disease, characterized by severe thickening of the palms and soles, caused by mutations in the keratin K9 (KRT9) gene. To date, a number of KRT9 mutations have been detected, most of which affect the highly conserved 1A region of the central alpha-helical domain, important for keratin heterodimerization. The most common mutation is the substitution of the arginine in position 163 with a tryptophan (R163W), which has been reported in North American, European, and Japanese populations. In a small number of cases, EPPK is associated with knuckle pad keratosis, but no correlation between this additional phenotype and a specific mutation has been found. Moreover, K9 is not normally expressed in knuckle skin, raising the question of the pathogenic mechanism leading to this additional phenotype. Here we show that in a family affected by EPPK and knuckle pad keratosis, carrying the R163W substitution, wild type (wt) and mutated K9 are strongly expressed in knuckle pads. These results suggest that the knuckle pad phenotype is due to ectopical expression of K9.
authors.affiliation: IDI-IRCCS Biochemistry laboratory c/o Dep. of Experimental Medicine, University of Tor Vergata, Via Montpellier, 1. 00133 Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Codispoti
authors.forename: Enrico
authors.initials: E
authors.lastname: Colombo
authors.forename: Loredana
authors.initials: L
authors.lastname: Zocchi
authors.forename: Valeria
authors.initials: V
authors.lastname: Serra
authors.forename: Ginevra
authors.initials: G
authors.lastname: Pertusi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Leigheb
authors.forename: Rossana
authors.initials: R
authors.lastname: Tiberio
authors.forename: Guido
authors.initials: G
authors.lastname: Bornacina
authors.forename: Riccardo
authors.initials: R
authors.lastname: Zuccoli
authors.forename: Antonio
authors.initials: A
authors.lastname: Ramponi
authors.forename: Elena
authors.initials: E
authors.lastname: Campione
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Terrinoni
mesh_terms: D005260:Female; D005385:Fingers / Q000002:abnormalities*; D006801:Humans; D007558:Italy; D053534:Keratin-9 / Q000235:genetics*; D053546:Keratoderma, Palmoplantar, Epidermolytic / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: D053534:Keratin-9