KERATIN-9 GENE-MUTATIONS IN EPIDERMOLYTIC PALMOPLANTAR KERATODERMA (EPPK)

We have isolated the gene for human type l keratin 9(KRT9) and localis ed it to chromosome 17q21. Patients with epidermolytic palmoplantar ke ratoderma (EPPK), an autosomal dominant skin disease, were investigate d. Three KRT9 mutations, N160K, R162Q, and R162W, were identified. All the mutations are in the highly conserved coil 1A of the rod domain, thought to be important for heterodimerisation. R162W was detected in five unrelated families and affects the corresponding residue in the k eratin 14 and keratin 10 genes that is also altered in cases of epider molysis bullosa simplex and generalised epidermolytic hyperkeratosis, respectively. These findings provide further evidence that mutations i n keratin genes may cause epidermolysis and hyperkeratosis and that hy perkeratosis of palms and soles may be caused by different mutations i n the KRT9 gene.