KERATIN-9 POINT MUTATION IN THE PEDIGREE OF EPIDERMOLYTIC HEREDITARY PALMOPLANTAR KERATODERMA PERTURBS KERATIN INTERMEDIATE FILAMENT NETWORK FORMATION

Keratins form an intracellular keratin filament network in keratinocyt es. Point mutations in the epidermal keratins could lead to the disrup tion of keratin filament formation, developing skin diseases such as e pidermolytic 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 EH PPK. Transfection into MDCK cells and DJM-1 cells revealed that the pl asmid CMX vector containing normal keratin 9 cDNA showed normal kerati n network formation, whereas the vector with a G to A point mutated ke ratin 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 formati on.