Epidermolysis bullosa simplex

A number of skin diseases, mainly characterized by blistering, have been found to be due to mutations in genes encoding various keratins. Three of these disorders are epidermolysis bullosa simplex, epidermolytic hyperkeratosis, and epidermolytic pahnoplantar kerato-derma. The blistering probably reflects a diminished capacity of various layers of the skin to resist mechanical stresses due to abnormalities in microfilament strucmre. 

Smith, T. A., Steinert, P. M., and Parry, D. A. D. (2004). Modeling effects of mutations in coiled-coil structures Case study using Epidermolysis Bullosa Simplex mutations in segment 1A of K5/K14 intermediate filaments. Proteins 55, 1043-1052. 

Gache, Y., Chavanas, S., Lacour, J. P., Wiche, G., Owaribe, K., Meneguzzi, G., and Ortonne, J. P. (1996). Defective expression of plectin/HDl in epidermolysis bullosa simplex with muscular dystrophy. /. Clin. Invest. 97, 2289-2298. 

Pulkkinen, L., Smith, F. J. D., Shimizu, H., Murata, S., Yaoita, H., Hachisuka, H., Nishikawa, T., McLean, W. H. I., and Uitto, J. (1996). Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Hum. Molec. Gent. 5, 1539-1546. 

Dillman et al. (2003) have recently shown that sulphur mustard causes keratin 14 and keratin 5 to clump into stable aggregates. These appear within 15 min of exposure to sulphur mustard. It was noted that a number of blistering disorders (epidermolysis bullosa simplex and epidermolytic hyperkeratosis) are associated with abnormalities of these keratin molecules (Fuchs et al, 1994). The role of keratin 14 in linking to plectin (another component of the hemidesmosomes) and to the bullous pemphigoid antigen le was also noted. Werrlein and Madren-Whalley (2000) demonstrated that sulphur mustard reduced expression of keratin 14... 

Fuchs E, Coulombe P, Cheng J et al. (1994). Genetic bases of epidermolysis bullosa simplex and epidermolytic hyperkeratosis. J Invest Dermatol, 103(Supplement 5), 25S-30S. 

In epidermolysis bullosa simplex, the skin blisters in response to a very slight mechanical stress. The familial form of the disease is generally caused by mutations in either of the two forms of keratin that constitute the keratin heterodimers of the basal layer of the epidermis. The weakened keratin cytoskeleton results in cytolysis when stress is applied. The disease also can be caused by mutations in plektin, the protein that attaches keratin to the membrane protein integrin in hemidesmosomes (a structure involved in attaching cells to the extracellular matrix). 

Fielding CJ, Fielding PE (2003) Relationship between cholesterol trafficking and signaling in rafts and caveolae. Bio-chim Biophys Acta 1610 219-228 Fine JD, Griffith RD (1985) A specific defect in glycosylation of epidermal cell membranes. Definition in skin from patients with epidermolysis bullosa simplex. Arch Dermatol 121 1292-1296... 

Ishida-Yamamoto A, McGrath JA, Chapman SJ et al (1991) Epidermolysis bullosa simplex (Dowling-Meara type) is a genetic disease characterized by an abnormal keratin-filament network involving keratins K5 and K14. J Invest Dermatol 97 959-968... 

Olaisen, B. and Gedde-Dahl, T. (1973). GPT-epidermolysis bullosa simplex (EBS Ogna) linkage in man. Hum. Hered., 23,189... 

Bullous diseases are rare diseases, occurring infrequently in young people and, today, effectively controlled by specific treatments (pemphigus, pemphigoid and dermatitis herpetiformis). Some types of epidermolysis bullosa, congenital (especially the simplex form) and acquired, must be mentioned since they... 

---