Plectin and human genetic disorders of the skin and muscle

Abstract Recent progress in understanding the molecular organization of the cutaneous basement membrane zone (BMZ) has revealed an intricate network of structural proteins necessary for stable association of the epidermis to the underlying dermis. Molecular genetics of the cutaneous BMZ has also revealed that defects in as many as nine distinct genes within the dermal‐epidermal junction which result in different forms of epidermolysis bullosa (EB). a group of heritable mechano‐bullous disorders. We have recently demonstrated that a variant of EB associated with late‐onset development of muscular dystrophy (EB‐MD. MIM no. 226670) results from mutations in the gene encoding plectin (PLEC1). a cytoskeleton associated attachment protein present in the hemidesmosomal inner plaque and the sarcolemma of the muscle. Consequently, mutations in this multi‐functional gene/protein system can result in phenotypic manifestations of EB‐MD both in the skin and the muscle. In this overview, we will summarize the domain organization of plectin and the structure of the corresponding gene (PLEC1). as well as the genetic basis of EB‐MD in families studied thus far. Elucidation of the molecular basis of this subtype of EB adds to our understanding of the structural and functional complexity of the cutaneous BMZ.