Epidermolysis bullosa simplex (EBS) comprises a group of hereditary disorders characterized by mechanical stress-induced blistering of the skin, which results from tissue separation within the epidermal basal keratinocy-

of hereditary disorders characterized by mechanical stress-induced blistering of the skin, which results from tissue separation within the epidermal basal keratinocytes (1). The most severe subtype is the Dowling-Meara type (EBS-DM); the moderately severe variant is other generalized (EBS, gen-nonDM) with generalized blister formation; and the mildest variant is localized with blistering confined to the hands and feet (1, 2). EBS is mostly inherited in an autosomal dominant fashion and is caused by a single mutation in either KRT5 or KRT14, which encode keratin 5 (K5) or keratin 14 (K14), respectively (3). K5/14 form heterodimers that assemble into intermediate filaments (IFs) of the basal keratinocytes (2). The amino acid sequences of K5/14 share a characteristic tripartite structure that includes a central α-helical rod domain flanked by non-α-helical Nand C-terminal end domains called the head and the tail, respectively (4). The α-helical rod domain consists of 4 segments (coils 1A, 1B, 2A and 2B) responsible for dimerization and higher-order polymerization, and it is interrupted by 3 non-helical linkers (L1, L1–2 and L2). The ends of the rod domain, known as the helix initiation motif (HIM) and the helix termination motif (HTM), are more highly conserved and have been known to be important areas for K5/14 to form heterodimers, stabilize the helix structure and assemble into filaments (5). Consequently, more severe EBS has been associated with mutations in HIM and HTM (3). In contrast, milder EBS is usually linked to mutations in less essential central rod domains, the L1-2 non-helical linker region, and the H1 region, which is immediately adjacent to the N-terminal end of coil 1A in K5 (3). In this study, we identified a p.Glu168Asp mutation at the boundary site between the H1 and coil 1A domains of K5 in an African family with EBS, gen-nonDM.