Genomic organization and amplification of the human epidermal type II keratin genes K1 and K5

Keratins are a family of structurally related proteins that form the intermediate filament cytoskeleton in epithelial cells. Mutations in K1 and K5 result in the autosomal dominant disorders epidermolytic hyperkeratosis/bullous congenital ichthyosiform erythroderma and epidermolysis bullosa simplex, respectively. Most disease-associated mutations are within exons encoding protein domains involved in keratin filament assembly. However, some mutations occur outside the mutation hot-spots and may perturb intermolecular interactions between keratins and other proteins, usually with milder clinical consequences. To screen the entire keratin 1 and keratin 5 genes we have characterized their intron-exon organization. The keratin 1 gene comprises 9 exons spanning approximately 5.6 kb on 12q, and the keratin 5 gene comprises 9 exons spanning approximately 6.1 kb on 12q. We have also developed a comprehensive PCR-based mutation detection strategy using primers placed on flanking introns followed by direct sequencing of the PCR products.