Keratin gene mutations in human skin disease
| Autor: | H. P. Stevens, M. H. A. Rustin |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Keratoderma
Palmoplantar Diffuse medicine.medical_specialty Positional cloning Hyperkeratosis Intermediate Filaments Gene Expression Mice Transgenic macromolecular substances Biology Skin Diseases Epidermolytic hyperkeratosis Mice Epidermolysis bullosa simplex Molecular genetics medicine Animals Humans Point Mutation Genetics Hyperkeratosis Epidermolytic Epidermolytic Palmoplantar Keratoderma integumentary system General Medicine medicine.disease Keratin 8 Keratins Epidermolysis bullosa Epidermolysis Bullosa Research Article |
| Zdroj: | Postgraduate Medical Journal. 70:775-779 |
| ISSN: | 1469-0756 0032-5473 |
| DOI: | 10.1136/pgmj.70.829.775 |
| Popis: | The molecular biology of these monogenetic skin diseases has been approached in two ways. The first was initiated by ultrastructural observations postulating mutations in the structural proteins of the cell so that linkage and keratin mutations could be extrapolated. The second approach has been by the use of transgenic mice technology to produce the phenotypes of human blistering skin diseases with specific keratin gene mutations. Over the last 10 years dermatology has been in the forefront of academic research examining the genetic basis of monogenetic diseases and has used the powerfully combined approaches of molecular biology, morphological studies, immunohistochemist.y and biochemical studies. The key to these developments has been the polymerase chain reaction (PCR) which has made linkage analysis and gene sequencing possible. The target genes for the hereditary genodermatoses were identified using biochemical, immunohistochemical and positional cloning techniques which has given molecular genetics the power to unravel the nature ofthe keratin gene mutations. Keratin mutations in a number of genodermatoses (epidermolytic hyperkeratosis; epidermolysis bullosa simplex, WeberCockayne, Koebner and epidermolytic palmoplantar keratoderma) have now been determined and all have two common features. The first, epidermolysis or blistering, is a prominent histological feature. Secondly, the mutations all lie in four highly conserved subdomains common to all the keratins. These subdomains are important in filament assembly. Mutations at these critical points result in perturbation of keratin assembly, and result in epidermolysis, seen in both the affected individuals as well as in transgenic mice. |
| Databáze: | OpenAIRE |
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