Nature Genetics
6, 174 - 179 (1994)
doi:10.1038/ng0294-174
Keratin 9 gene mutations in epidermolytic palmoplantar keratoderma (EPPK)André Reis1, Hans-Christian Hennies1, Lutz Langbein2, Martin Digweed1, Dietmar Mischke3, Matthias Drechsler4, Evelin Schröck4, Brigitte Royer-Pokora4, Werner W. Franke2, Karl Sperling1
& Wolfang Küster5
1Institute of Human Genetics, Free University, Heubnerweg 6, D-14059 Berlin, Germany
2Division of Cell Biology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany
3Institute of Experimental Oncology and Transplantation Medicine, Free University, Spandauer Damm 130, D-14050 Berlin, Germany
4Institute of Human Genetics, University Heidelberg, Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany
5Department of Dermatology, University Marburg, Deutschhausstr. 9, D-35037 Marburg, Germany Correspondence should be addressed to A.R. We have isolated the gene for human type I keratin 9 (KRT9) and localised it to chromosome 17q21. Patients with epidermolytic palmoplantar keratoderma (EPPK), an autosomal dominant skin disease, were investigated. 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 keratin 14 and keratin 10 genes that is also altered in cases of epidermolysis bullosa simplex and generalised epidermolytic hyperkeratosis, respectively. These findings provide further evidence that mutations in keratin genes may cause epidermolysis and hyperkeratosis and that hyperkeratosis of palms and soles may be caused by different mutations in the KRT9 gene.
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