A site-specific plectin mutation causes dominant epidermolysis bullosa simplex Ogna: two identical de novo mutations

Abstract

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.