Abstract: Objective:To understand the pathogenic variation spectrum and the hotspot variation of COL7A1 gene in epidermolysis bullosa (EB), and to analyze the correlation between different inheritance patterns of COL7A1 gene and the severity of skin lesions in neonatal period. Methods:We collected neonates diagnosed as EB caused by COL7A1 gene pathogenic or likely pathogenic variants detected by high-throughput sequencing from Department of Neonatology of Children's Hospital of Fudan University.The clinical manifestations of them were summarized, and the phenotype-genotype correlation was analyzed. Results:A total of 28 EB newborns were enrolled including 5 cases of autosomal dominant(AD) inheritance and 23 cases of autosomal recessive(AR) inheritance. There was no significant difference between AD and AR mode EB in skin lesions, skin loss and other clinical findings. There was no statistically significant difference between the initial stage and the extreme stage of skin lesions in AD mode EB (χ2=0.668, P=0.414). The skin lesions in AR mode EB at the initial stage were significantly different from those at the extreme stage (χ2=16.896, P<0.01). There was no significant difference in the percentage of skin lesions in AD mode EB and AR mode EB in the initial and extreme stages of disease (P=0.131, P=0.071). Fifty-four COL7A1 pathogenic variants were detected, including 30 (55.6%) known pathogenic variants, 21 novel pathogenic variants and 3 with unclear clinical significance. The hotspot pathogenic variants were c.8569G>T(p.E2857X) in 4 cases, c.3625_3636delinsC(p.S1209Lfs*6) in 3 cases and c.4089_4090delinsC(p.P1364Lfs*35) in 3 cases. Conclusion:It has no characteristic changes in skin lesions, skin loss and other clinical findings between different inheritance (AR or AD) in EB caused by pathogenic variation of COL7A1 gene in neonatal period. The scope of skin findings of AR mode in the extreme stage is more extensive than that in the initial stage.