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.

A 60-year-old male patient developed progressive wound ulcerations, simulating wound sepsis after coronary bypass operation. The condition did not respond to intensive antibiotic therapy. Based on clinical signs and biopsy, the diagnosis of pyoderma gangrenosum was made and successfully treated with cyclosporin A. Pyoderma gangrenosum, although extremely rare, must be considered as a possible diagnosis in wound complications unresponsive to traditional therapy.

Epidermolysis bullosa (EB) is a heterogeneous group of genetic bullous skin diseases. The EB simplex group (EBS) is characterized by intraepidermal blistering. EBS-Ogna was first described as a separate entity based on clinical studies. Later genetic linkage of EBS-Ogna to the GPT locus for glutamate pyruvate transaminase (alanine transaminase) was detected and GPT was assigned to chromosome 8, then to the terminal long arm band 8q24. Plectin is an abundant and widespread cytoskeletal protein which has been proposed as a general crosslinking element of intermediate filaments. Human plectin has recently been cloned and in situ hybridized to chromosome 8q24. To examine whether plectin could be associated with EBS-Ogna we performed an immunohistochemical study with a panel of mAbs to rat plectin. Interestingly, 2 of these mAbs showed strong intracellular staining of the suprabasal and basal layer of the epidermis in all control samples, whereas no reactivity of the basal layer was found in the Ogna group. These results strongly suggest that plectin is involved in the pathogenesis of EBS-Ogna.