Mapping of a gene for epidermolytic palmoplantar keratoderma to the region of the acidic keratin gene cluster at 17q12-q21.
Epidermolytic palmoplantar keratoderma (EPPK) (Vörner-Unna-Thost) is an autosomal dominantly inherited skin disease of unknown etiology characterized by diffuse severe hyperkeratosis of the palms and soles and, histologically, by cellular degeneration. We have mapped a gene for EPPK to chromosome 17q11-q23, with linkage analysis using microsatellite DNA-polymorphisms, in a single large family of 7 generations. A maximum lod score of z = 6.66 was obtained with the probe D17S579 at a recombination fraction of theta = 0.00. This locus maps to the same region as the type I (acidic) keratin gene cluster. Keratins, members of the intermediate filament family, the major proteins of the cytoskeleton in epidermis, are differentially expressed in a tissue-specific manner. One acidic keratin, keratin 9 (KRT9), is expressed only in the terminally differentiated epidermis of palms and soles. The KRT9 gene has not yet been cloned; however, since the genes for most acidic keratins are clustered, it is highly probable that it too will map to this region. We therefore propose KRT9 as the candidate gene for EPPK.
Reis
A
A
Institut für Humangenetik, Freie Universität Berlin, Federal Republic of Germany.
Küster
W
W
Eckardt
R
R
Sperling
K
K
D002886:Chromosomes, Human, Pair 17; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D007633:Keratins / Q000235:genetics*; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics
D007633:Keratins