Yueqian Yu, Zhenzhen Wang, Zihao Mi, Lele Sun, Xi'an Fu, Gongqi Yu, Zheng Pang, Hong Liu, Furen Zhang
DOI: 10.2340/00015555-3843

Epidermolysis bullosa encompasses a group of inherited blistering skin disorders. The pathogenic mutations in 10–25% of patients with epidermolysis bullosa have not been identified by Sanger sequencing. The aims of this study were to identify the pathogenic sequence alterations in a large cohort of Chinese patients with epidermolysis bullosa and to clarify the relationship between clinical phenotypes and genotypes. Whole-exome sequencing was performed on 44 pedigrees and 13 sporadic cases. The results were further confirmed by Sanger sequencing. In total, 52 mutations, comprising 19 novel and 33 previously reported mutations, were identified in 5 genes, with a mutation detection rate of 100%. A relationship between subtypes and pathogenic genes was established: 12 cases of epidermolysis bullosa simplex were associated with mutations in KRT5/14 and PLEC; one case of junctional epidermolysis bullosa carried mutations in ITGB4; and 44 cases of dystrophic epidermolysis bullosa were caused by mutations in COL7A1. The results of this study support whole-exome sequencing as a promising tool in the genetic diagnosis of epidermolysis bullosa.

Epidermolysis bullosa is a rare inherited skin disorder. According to previous reports, immunofluorescence mapping established the epidermolysis bullosa subtype in 76% of cases, while the molecular pathology was identified in 90% of cases by the targeted next-generation sequencing panel. The detection rate of pathogenic genes and mutations in 57 Chinese patients with epidermolysis bullosa in this study was 100% by whole-exome sequencing. A total of 52 pathogenic mutations were found in 5 genes, of which 25 were new mutations. The phenotype-genotype correlation was established in all cases. The results of this study suggest that whole-exome sequencing improves genetic diagnostic sensitivity in epidermolysis bullosa.

Figure S1