There are 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, lamella ichthyosis, bullous- and non-bullous 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 involved a collaboration with the primary genetic studies work of Dr. Bale (see project number Z01 AR 41089-01). Following identification of suitable families, linkage analyses 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 data, we have characterized the genetic (a leucine-to-proline mutation of the keratin 1 chain) in one family of the autosomal dominant disorder BCIE.
