Desmoglein 3 (Dsg3), encoded by DSG3 gene, is the major component of desmosomes which contribute to cell-cell adhesion in epidermis. Autoantibodies against human Dsg3, called as mucosal pemphigus vulgaris, lead to suprabasal acantholysis histologically and blister formation limited to the mucosa clinically. A patient with Dsg3 deficiency, however, has never been reported. Here, we describe a new hereditary disease featuring recurrent mucosal erosions caused by homozygous mutation in DSG3. A 1 year-old female baby presented with recurrent erosions in the oral and laryngeal mucosa after birth. Histological examination of skin biopsy showed suprabasal acantholytic blisters. Direct immunofluorescence staining, indirect immunofluorescence and ELISA for Dsg 1 and 3 were negative. Whole genome sequencing from her DNA identified a novel homozygous nonsense mutation in DSG 3. Using direct sequencing and restriction fragment length polymorphism, we found that her parents harbor the heterozygous mutations in DSG3. Immunofluorescence showed that Dsg3 was not observed in her skin as well as oral mucosa. Electron microscopy of her skin biopsy shows mature desmosomes in the basal layer. Therefore, we reported the first case of a nonsense mutation in human DSG3.