Abstract: 【Abstract】 Objective To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa, and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients. Methods DNA was extracted from peripheral blood samples of two family members, and subjected to high-throughput sequencing and Sanger sequencing. Results The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa, and the symptoms of the proband in family 1 were more serious than those of other patients in the family. Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C （p.G2028R） in the COL7A1 gene, and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2 （IVS91） T>G in the COL7A1 gene, both of which were first reported. The proband in family 2 carried a mutation c.6081_6082 ins C （p.G2028Rfs*71） and the first reported mutation c.1892G>A （p.W631X） in the COL7A1 gene, which were inherited from her father and mother, respectively. Conclusion The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1; the first reported mutations enriched the mutation spectrum of the COL7A1 gene.

Key words: Epidermolysis bullosa, junctional, DNA mutational analysis, Skin manifestations, Whole exome sequencing, COL7A1 gene