Mapping of a gene for epidermolytic palmoplantar keratoderma to the region of the acidic keratin gene cluster at 17q12?q21

Abstract

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.

Tissue Typing by Means of PCR and Capillary Electrophoresis: New Aspects, Reality and Issues

“…Корнеодесмоин (ко-дируемый геном CDSN), локализован в корнеодесмосомах ороговевающего и плоского эпителия волос и участвует в процессах его созревания [31,32]. В отношении KRT9 установлено, что он принимает участие в организации кератиновых филаментов и специфично экспрессируется в подошвенном и ладонном эпителии [33,34].…”

The Genetics of Human Skin Disease

“…In the case of epidemolytic palmoplantar keratoderma (EPPK), an autosomal dominant skin disease marked by hyperkeratosis on the palms and soles, the etiology had not previously determined through the use of ultrastructural or histological methods. Reis et al (1992) mapped the gene to chr17q11-23 using linkage with microsatellite markers in a kindred of seven generations, obtaining a LOD score of Z ¼ 6.66 at a recombination fraction (u) of 0. Interestingly, the type I (acidic) keratin cluster of genes map to this region and the KRT9 gene was deduced to be the candidate gene because it mapped to this region and is the only keratin to be specifically expressed in the terminally differentiated epidermis of palms and soles-the sites of pathology for the EPPK phenotype (Reis et al 1992).…”

“…Reis et al (1992) mapped the gene to chr17q11-23 using linkage with microsatellite markers in a kindred of seven generations, obtaining a LOD score of Z ¼ 6.66 at a recombination fraction (u) of 0. Interestingly, the type I (acidic) keratin cluster of genes map to this region and the KRT9 gene was deduced to be the candidate gene because it mapped to this region and is the only keratin to be specifically expressed in the terminally differentiated epidermis of palms and soles-the sites of pathology for the EPPK phenotype (Reis et al 1992). Importantly, subsequent investigation led to the identification of several mutations within the rod domain of the KRT9 gene in unrelated kindreds (Reis et al 1994).…”

Hiperqueratose palmo-plantar epidermolítica (Vörner) relato de caso e revisão da literatura

“…15,16 Tal alteração geralmente ocorre na região central, não variável, bed, however, for the above-mentioned reasons, such disease is probably little notified, 13 and even considered by some authors to be the most common form of palmoplantar keratoderma. 13 The real significance of the epidermolysis, however, is still uncertain and does not occur exclusively in this variant, but also in other keratodermas, as well as other congenital and acquired diseases (Table 6).…”