Keratin 9 mutations in the coil 1A region in epidermolytic palmoplantar keratoderma

The palmoplantar keratodermas (PPK) are a heterogeneous group of conditions , most frequently inherited in autosomal dominant fashion. A few are well-d ocumented autosomal recessive disorders; other are acquired in association with certain metabolic disorders and malignancies. Recently different point mutations of the keratin 9 (K9) gene have been identified in unrelated fam ilies with epidermolytic palmoplantar keratoderma (EPPK). We investigated t wo unrelated Hungarian families with EPPK. In one, a mutation consisting of a G-->A transversion at nucleotide position 551, which changes codon argin ine to glutamine at codon 162 (R162Q), was found. In the other, we observed a novel mutation at nucleotide position 571, which changes codon 169 lysin e (AAG) into the amber stop codon (TAG) (K169X). Each found mutation is pre sent in the highly conserved coil 1A region of the rod domain. In the case of a stop codon type of mutation, it is questionable whether it really resu lts in a clinical phenotype, but segregation analysis revealed cosegregatio n of the PPK phenotype with the. mutant allele.