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 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin. The study of keratin diseases has led to a better understanding of the importance of the intermediate filament cytoskeleton and associated connector molecules in maintaining the structural integrity of the epidermis and other high stress epithelial tissues, as well as allowing diagnosis at the molecular level thus facilitating prenatal testing for this heterogeneous group of genodermatoses.
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PMID:Human keratin diseases: hereditary fragility of specific epithelial tissues. 902 91

Keratins are obligate heterodimer proteins that form the intermediate filament cytoskeleton of all epithelial cells. Keratins are tissue and differentiation specific and are expressed in pairs of types I and II proteins. The spectrum of inherited human keratin diseases has steadily increased since the causative role of mutations in the basal keratinocyte keratins 5 and 14 in epidermolysis bullosa simplex (EBS) was first reported in 1991. At the time of writing, mutations in 15 epithelial keratins and two trichocyte keratins have been associated with human diseases which include EBS, bullous congenital ichthyosiform erythroderma, epidermolytic palmoplantar keratoderma, ichthyosis bullosa of Siemens, diffuse and focal non-epidermolytic palmoplantar keratoderma, pachyonychia congenita and monilethrix. Mutations in extracutaneous keratins have been reported in oral white sponge naevus and Meesmann's corneal dystrophy. New subtleties of phenotype-genotype correlation are emerging within the keratin diseases with widely varying clinical presentations attributable to similar mutations within the same keratin. Mutations in keratin-associated proteins have recently been reported for the first time. This article reviews clinical, ultrastructural and molecular aspects of all the keratin diseases described to date and delineates potential future areas of research in this field.
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PMID:Human keratin diseases: the increasing spectrum of disease and subtlety of the phenotype-genotype correlation. 1035 17

Keratins are the type I and II intermediate filament proteins which form a cytoskeletal network within all epithelial cells. They are expressed in pairs in a tissue- and differentiation-specific fashion. Epidermolysis bullosa simplex (EBS) was the first human disorder to be associated with keratin mutations. The abnormal keratin filament aggregates observed in basal cell keratinocytes of some EBS patients are composed of keratins K5 and K14. Dominant mutations in the genes encoding these proteins were shown to disrupt the keratin filament cytoskeleton resulting in cells that are less resilient and blister with mild physical trauma. Identification of mutations in other keratin genes soon followed with attention focussed on disorders showing abnormal clumping of keratin filaments in specific cells. For example, in bullous congenital ichthyosiform erythroderma, clumping of filaments in the suprabasal cells led to the identification of mutations in the suprabasal keratins, K1 and K10. Mutations have now been identified in 18 keratins, all of which produce a fragile cell phenotype. These include ichthyosis bullosa of Siemens (K2e), epidermolytic palmoplantar keratoderma (K1, K9), pachyonychia congenita (K6a, K6b, K16, K17), white sponge nevus (K4, K13), Meesmann's corneal dystrophy (K3, K12), cryptogenic cirrhosis (K8, K18) and monilethrix (hHb6, hHb1).In general, these disorders are inherited as autosomal dominant traits and the mutations act in a dominant-negative manner. Therefore, treatment in the form of gene therapy is difficult, as the mutant gene needs to be inactivated. Ways of achieving this are actively being studied. Reliable mutation detection methods from genomic DNA are now available. This enables rapid screening of patients for keratin mutations. For some of the more severe phenotypes, prenatal diagnosis may be requested and this can now be performed from chorionic villus samples at an early stage of the pregnancy. This review article describes the discovery of, to date, mutations in 18 keratin genes associated with inherited human diseases.
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PMID:The molecular genetics of keratin disorders. 1268 39

Epidermolytic hyperkeratosis is a histological reaction pattern seen in a variety of disease processes, including epidermolytic ichthyosis, Vorner's epidermolytic palmoplantar keratoderma, epidermal nevus, and solitary epidermolytic acanthoma. Here we present the case of a 59-year-old woman with multiple asymptomatic papules on her vulva. Clinical differential diagnoses included condyloma acuminata, seborrheic keratoses, bowenoid papulosis, adnexal tumors, and papular acantholytic dyskeratosis. Shave biopsy revealed findings consistent with epidermolytic hyperkeratosis. This case represents an interesting presentation of focally disseminated vulvar epidermolytic acanthomas and highlights the importance of a biopsy in establishing this diagnosis.
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PMID:Presentation of epidermolytic acanthomas as multiple tan papules on the vulva. 2703 69