Although various types of mutations have been identified in COL7A1 of patients with RDEB, there is no evidence for hot spot mutations in this gene. In this study, we performed mutation analysis in COL7A1 of 15 unrelated Japanese RDEB patients, and we have identified two common mutations in exon 81 (6576+1 G to C) and in exon 116 (8572 G to T). Four out of the 15 patients share the former mutation which induce aberrant splicing in intron following exon 81, resulting in formation of premature termination codon (PTC) in further downstream. Another 4 patients possess the latter mutation which introduce PTC at the position of E of 2558 (E 2558 X). One patient who have both of these two mutations exhibit relatively severe blistering with less syndactyly. Further analysis is required to determine whether these two mutations are Japanese hot spots or originated from Japanese common ancestor genes.