Elsevier

Clinics in Dermatology

Volume 23, Issue 1, January–February 2005, Pages 6-14
Clinics in Dermatology

Inherited defects in keratins

https://doi.org/10.1016/j.clindermatol.2004.09.014Get rights and content

Abstract

In the years following the initial reports of keratin gene mutations in epidermolysis bullosa simplex, great strides have been made in understanding the basic biology of human keratins and in understanding the etiology and pathogenesis of a number of specific human single gene disorders. A total of 19 human keratin genes is now linked to specific diseases. This article summarizes current knowledge in relation to basic keratin biology, known disease associations, and genotype correlation in this diverse and complex group of conditions.

Section snippets

Keratins: basic biology

The cytoplasm of animal cells is structured by scaffolding composed of actin microfilaments, microtubules, and intermediate filaments. The largest group within the intermediate filament family is the keratins (types I and II intermediate filament proteins), which are expressed specifically in the cytoplasm of epithelial cells where they form a dense meshwork of 10-nm filaments (Fig. 1).1 In 1977, work on sheep wool keratins had suggested a classification of keratins into 2 subtypes. This

Genetic disorders due to mutations in human keratins

Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures (Table 1). Epidermolysis bullosa simplex (EBS) was the first keratin disease to be identified with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma and resulting in skin fragility.7., 8., 9. Since mutations were identified in the basal cell keratins, the total number of keratin genes

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