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The collagenase production of cultured skin fibroblasts from Scandinavian families with dominant (D-EBD) and recessive (R-EBD) epidermolysis bullosa dystrophica has been investigated. Heterogeneity as a result of body location origin has been ruled out as fibroblasts obtained from predilection sites produce the same amount of immunoreactive collagenase as those obtained from non-predilection sites of the same subjects. Large variations in in vitro collagenase production were found between individuals and families. Within the R-EBD group, four out of eighteen patients showed an in vitro elevated level of immunoreactive collagenase compared to their healthy relatives, other EB types, and the control group. This shows that an in vitro elevated collagenase production is not a marker for the entire disease group and that the disease denoted as R-EBD probably is etiologically and pathogenetically heterogeneous. [ABSTRACT FROM AUTHOR]

The use of gelatinase expression in dermal fibroblast cultures as a marker for generalized epidermolysis bullosa simplex (D-EBS-Köbner) has been tested. None of the 6 Köbner patients tested (from 3 families) produced reduced amounts of gelatinase compared with their healthy relatives and other control groups. This shows that a reduced production of gelatinase from dermal fibroblasts is not uniformly a marker for D-EBS-K. [ABSTRACT FROM AUTHOR]

The article focuses on clinical heterogeneity in epidermolysis bullosa (EB). A recent article presented an extensive review on the role of anchoring fibril changes in dystrophic epidermolysis bullosa, summarizing electron microscopic, biochemical and other evidence. Included were highly relevant points on clinical diagnosis, not the least of which was the difficulty in discriminating the local forms of the recessive type from sporadic dominant mutant cases. The focus in the article is on the clinical variations in different categories of EB, their possible causations, and consequences.

Plectin is one of the largest and most versatile cytolinker proteins known. In basal keratinocytes it links the intermediate filament network to cell membrane-associated hemidesmosomes. Several mutations in its gene have been identified that lead to the recessive disease epidermolysis bullosa with muscular dystrophy. We report here a mutation that leads to a dominant form of the disease, epidermolysis bullosa simplex Ogna. We found that the epidermolysis bullosa simplex Ogna phenotype is due to a site-specific missense mutation within plectin's rod domain. Further, we show that epidermolysis bullosa simplex Ogna is not restricted to a single Norwegian kindred as previously believed. A German family with the phenotypic hallmarks of epidermolysis bullosa simplex Ogna was found to carry an identical de novo mutation. These two mutations arose about 200 y apart in time. Consistent with the absence of muscular symptoms in these patients, muscle biopsies from several epidermolysis bullosa simplex Ogna members of the Norwegian kindred showed normal staining patterns using antibodies to plectin. Skin changes in epidermolysis bullosa simplex Ogna patients are documented on the ultrastructural level. [ABSTRACT FROM AUTHOR]

Epidermolytic hyperkeratosis is a rare autosomal dominant inherited skin disorder caused by keratin 1 or keratin 10 mutations. Keratins are major structural proteins of the epidermis, and in keratinocytes committed to terminal differentiation the intermediate filaments are composed of keratin 1 and keratin 10 heterodimers. The majority of reported mutations (86.6%) are heterozygous single point mutations and most of these are located in the 1A and 2B regions of the highly conserved keratin alpha-helical rod domain. We have studied eight Scandinavian families with epidermolytic hyperkeratosis and identified three point mutations, two codon deletions, two splice site mutations, and a complex deletion/insertion. Two of the point mutations were in the KRT1 gene (F191C and K177N) and the other was in KRT10 (L453P). All three patients had associated palmoplantar keratoderma. The splice site mutations in KRT1 both caused a large deletion removing 22 codons (delta176-197) from the 1A helical domain. Codon deletions were found in KRT1 (delta170-173) and in KRT10 (delta161-162) in two patients with a severe phenotype. A final patient had a more complex mutation with a large deletion (442 bp) together with a large insertion (214 bp) of unknown origin that caused deletion of exon 6 in KRT1. In conclusion, we have found eight novel keratin mutations that cause epidermolytic hyperkeratosis with differing phenotypes. Even when a large part of keratin 1 (46 amino acids) is deleted, surprisingly mild phenotypes can result, suggesting that genotype-phenotype relationships in epidermolytic hyperkeratosis are complex and do not solely depend on the type of mutation but also depend on interactions between the behavior of the mutant protein and the cellular environment.