title: Keratin 9 point mutation in the pedigree of epidermolytic hereditary palmoplantar keratoderma perturbs keratin intermediate filament network formation.
abstract: Keratins form an intracellular keratin filament network in keratinocytes. Point mutations in the epidermal keratins could lead to the disruption of keratin filament formation, developing skin diseases such as epidermolytic hereditary palmoplantar keratoderma (EHPPK). We found a G to A transition in keratin 9 (K9) cDNA, resulting in the substitution of glutamine for arginine at 162, in all patients of a pedigree of EHPPK. Transfection into MDCK cells and DJM-1 cells revealed that the plasmid CMX vector containing normal keratin 9 cDNA showed normal keratin network formation, whereas the vector with a G to A point mutated keratin 9 cDNA showed disrupted keratin filaments with droplet formation in the cells. These results indicate that the point mutation seen in our patients had a dominant-negative effect on keratin network formation.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kobayashi
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: N
authors.initials: N
authors.lastname: Matsuyoshi
authors.forename: S
authors.initials: S
authors.lastname: Imamura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D004285:Dogs; D005260:Female; D015870:Gene Expression; D006801:Humans; D007382:Intermediate Filaments / Q000473:pathology*; D007633:Keratins / Q000235:genetics* / Q000378:metabolism; D007645:Keratoderma, Palmoplantar / Q000235:genetics* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation
chemical_list: D007633:Keratins; D004247:DNA