There is a number of heritable diseases of cornification of human epidermis, which affect the suprabasal cell layers of the epidermis. These include the various ichthyoses (such as ichthyosis vulgaris, lamellar ichthyosis, bullous- and nonbullous congenital ichthyosiform erythroderma) and others including Darier's disease, Hailey-Hailey disease, etc. In all cases, these diseases follow simple or relatively simple genetic expression characteristics implying they involve simple mutations in one (or more) proteins expressed in epidermal cells committed to terminal differentiation. Although some morphological and biochemical analyses have been performed on several of these, in no case has the underlying genetic defect been identified. This project involves a collaboration with the primary genetic studies work of Dr. Bale (see project number Z01 AR 41089-02). Following identification of suitable families, linkage analyzes will be performed using PCR mapping of polymorphisms of candidate and other gene products of known location, to be followed by identification of the specific mutations in the genes that cause these occurrences of the disease. To date, we have identified a total of 10 mutations in either the keratin 1 - keratin 10 chains in separate families with epidemiolytic hyperkeratosis.
