Nevertheless, it is clear that skin blistering is either mild or absent in this disorder and thus whether the phenotypic consequences ofITGA3mutations should remain as part of the designated spectrum of EB, defined as a group of inherited blistering skin diseases, or not, is debatable. == CONCLUSIONS == This review has described the salient clinical and molecular features associated with three recently described forms of EB. new forms of EB is reviewed with respect to the initial gene discovery, clinical features, the current mutation database, and skin pathology. Awareness of these recently described forms of EB is helpful in the clinical evaluation of patients with EB and in defining genotype-phenotype correlation for inherited blistering skin Toll-Like Receptor 7 Ligand II diseases. Keywords: Basement membrane, Blister, Epidermolysis bullosa, Hemidesmosome, Mutation, Transport vesicles == INTRODUCTION == Over the past 25 years, enormous advances have been made in understanding the clinical and molecular basis of epidermolysis bullosa (EB); new phenotypes have been described, molecular insights have been gained, and translational research has launched innovative clinical trials of new cell- and gene-based therapies1. Summarizing recent data, a schematic of the protein/structural pathology currently implicated in the pathophysiology of EB is shown inFig. 1 . Concerning disease taxonomy, several attempts have been made to classify and reclassify EB, with helpful guidelines published by an international consensus group2. Although elements of the current classification of EB are still based on the level of blister formation at or within the dermal-epidermal junction or epidermis, these latest guidelines introduced an “onion skin” classification, providing a workable diagnostic algorithm based on variable access to general or specialized skin and molecular laboratory tests2. Most people with EB can now be classified into one of the existing disease categories, although, over the past few years several new clinicopathologic entities have been added to the collection of EB disorders. These newly reported conditions are often very rare and affect just a few individuals or families. Nevertheless, identification and recognition of these distinct clinicopathologic entities is important in improving clinical skills and gaining better insight into the pathophysiology of skin blistering and the macromolecular intricacies of adhesion and signaling that maintain healthy skin3. Toll-Like Receptor 7 Ligand II This review focuses on three relatively recent discoveries in EB. All CCND1 three disorders are autosomal recessive, and comprise two forms of EB simplex and one of junctional EB with extracutaneous abnormalities, which result from biallelic mutations inDST-e, EXPH5, orITGA3, respectively. This review describes the discovery of these conditions, outlines the clinical manifestations, summarizes the current known mutations, and places the discoveries in the context of skin pathology and the pathophysiology of blistering. == Fig. 1 . The molecular basis of epidermolysis bullosa. Mutations in structural components of hemidesmosomes, desmosomes, corneodesmosomes, intermediate filaments, actin microfilaments, focal contacts, and cell vesicle transport underlie a spectrum of skin fragility phenotypes. == == DST-e: autosomal recessive epidermolysis bullosa simplex == Pathogenic mutations inDST-ewere first reported in 20104. Their discovery followed identification of a parent-related Kuwaiti family with a relatively minor form of acral skin blistering. The clues to diagnosis came from transmission electron microscopy: the patient’s skin was completely lacking in hemidesmosomal inner plaques, raising the possibility that the inherent gene pathology lay in a protein normally sited within this part of the hemidesmosomal complex. A candidate gene approach with immunofluorescence microscopy and antibodies to various hemidesmosomal inner Toll-Like Receptor 7 Ligand II plaque components demonstrated a complete absence of immunostaining for the 230 kDa bullous pemphigoid antigen (BP230). Sanger sequencing ofDST-e, which encodes the BP230 protein, also known as epidermal dystonin, revealed a homozygous nonsense mutation, thus establishing a new form of autosomal recessive EB simplex with loss-of-function mutations inDST-e. == DST-e: clinical features == To date, six individuals from six different families with autosomal recessive EB simplex due toDST-epathology have been reported; five individuals were from Kuwait, the other patient was from Iran. All were Toll-Like Receptor 7 Ligand II from parent-related families. In most cases, blistering began at or shortly after birth. The blistering differed from more classic localized forms of EB simplex associated with mutations in keratin 5 (KRT5) and keratin 14 (KRT14), on the basis that some of the blisters were not directly related to pressure points on the soles Toll-Like Receptor 7 Ligand II of the feet or toes and the blisters were somewhat larger (up to several centimeters in diameter). The sides or.