title: Ultrastructural changes resulting from keratin-9 gene mutations in two families with epidermolytic palmoplantar keratoderma.
abstract: Palmoplantar keratoderma of Voerner type (or epidermolytic palmoplantar keratoderma) is an autosomal dominant inherited disorder of keratinization with histologic features of epidermolytic hyperkeratosis. We studied members of two large unrelated kindreds with epidermolytic palmoplantar keratoderma, and biopsy specimens of lesional palmar skin from both families confirmed the histologic changes of epidermolytic hyperkeratosis. Whorls of abnormally aggregated keratin filaments were seen ultrastructurally to be associated with signs of cellular disintegration in spinous and granular cells. Direct sequencing of genomic DNA samples obtained from several members of each family established the substitution of a highly conserved arginine by tryptophan (R162W) in the 1A region of the alpha-helical rod domain of keratin 9. This arginine residue in a highly conserved region of keratins 1 and 10 is affected by disruptive missense point mutations in many patients with bullous ichthyosiform erythroderma. An equivalent position in the sole and palm restricted keratin 9 appears to be the mutation hot spot in epidermolytic palmoplantar keratoderma. To date, R162W is the most prevalent genetic defect reported in this genodermatosis.
authors.affiliation: Experimental Dermatology Research Laboratories, London Hospital Medical College, England.
authors.forename: H A
authors.initials: HA
authors.lastname: Navsaria
authors.forename: O
authors.initials: O
authors.lastname: Swensson
authors.forename: R C
authors.initials: RC
authors.lastname: Ratnavel
authors.forename: M
authors.initials: M
authors.lastname: Shamsher
authors.forename: W H
authors.initials: WH
authors.lastname: McLean
authors.forename: E B
authors.initials: EB
authors.lastname: Lane
authors.forename: D
authors.initials: D
authors.lastname: Griffiths
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: I M
authors.initials: IM
authors.lastname: Leigh
mesh_terms: D001482:Base Composition; D005192:Family Health; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000648:ultrastructure; D007633:Keratins / Q000235:genetics* / Q000648:ultrastructure; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012867:Skin / Q000473:pathology
chemical_list: D007633:Keratins