title: Genomic organization and amplification of the human epidermal type II keratin genes K1 and K5.
abstract: 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.
authors.affiliation: Department of Cell and Molecular Pathology, St. John's Institute of Dermatology, London, United Kingdom. neil.2.whittock@kcl.ac.uk
authors.forename: N V
authors.initials: NV
authors.lastname: Whittock
authors.forename: R A
authors.initials: RA
authors.lastname: Eady
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005091:Exons; D006801:Humans; D007438:Introns; D007633:Keratins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary
chemical_list: D018076:DNA, Complementary; D007633:Keratins