Mutational analysis of epidermolysis bullosa in Taiwan by whole-exome sequencing complemented by RNA sequencing: a series of 77 patients

Wei Ting Tu, Ping Chen Hou, Peng Chieh Chen, Wan Rung Chen, Hsin Yu Huang, Jing Yu Wang, Yi Ting Huang, Yi Huei Wu, Chun Lin Su, Yen An Tang, Hiroaki Iwata, Ken Natsuga, Sheau Chiou Chao, H. Sunny Sun, Ming Jer Tang, Julia Yu Yun Lee, John A. McGrath, Chao Kai Hsu

Research output: Contribution to journalArticlepeer-review


Background: Epidermolysis bullosa (EB) is a heterogeneous group of hereditary skin diseases characterized by skin fragility. Primary data on Taiwanese population remain scarce. Methods: We gathered clinical information from EB patients at National Cheng Kung University Hospital from January, 2012, to June, 2021. Diagnostic tests including transmission electron microscopy, immunofluorescence studies, and whole-exome sequencing (WES) were performed. The pathogenicity of novel splice-site mutations was determined through reverse transcriptase-PCR of skin mRNA followed by Sanger and/or RNA sequencing. Results: Seventy-seven EB patients from 45 families were included: 19 EB simplex, six junctional EB, and 52 dystrophic EB. Pathogenic variants were identified in 37 of 38 families (97.4%), in which WES was used as a first-line tool for mutational analysis; RNA sequencing determined pathogenic variants in the remaining one family. A total of 60 mutations in EB-related genes were identified, including 22 novel mutations. The mutations involved KRT5, KRT14, PLEC, COL17A1, LAMB3, LAMA3, ITGB4, and COL7A1. Over one-quarter of DEB patients had EB pruriginosa. Conclusions: The distinct clinical presentation and molecular pathology of EB in Taiwan expand our understanding of this disorder. WES was an effective first-line diagnostic tool for identifying EB-associated variants. RNA sequencing complemented WES when multiple potentially pathogenic splice-site mutations were found.

Original languageEnglish
Article number451
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 2022 Dec

All Science Journal Classification (ASJC) codes

  • Genetics(clinical)
  • Pharmacology (medical)


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