Expression signature of epidermolysis bullosa simplex

Hum Genet. 2012 Mar;131(3):393-406. doi: 10.1007/s00439-011-1077-7. Epub 2011 Aug 30.


Epidermolysis bullosa simplex (EBS) is a skin disorder resulting from a weakened cytoskeleton of the proliferative compartment of the epidermis, leading to cell fragility and blistering. Although many mutations have been identified in intermediate filament keratins KRT5 and KRT14, detailed pathogenic mechanisms and the way these mutations affect cell metabolism are unclear. Therefore, we performed genomic and transcriptomic study in six Canadian EBS patients and six healthy subjects. We first characterized these patients at the genetic level and identified six pathogenic mutations of which two were novel. Then, we performed an expression microarray analysis of the EBS epidermis tissue to identify potential regulatory pathways altered in this disease. Expression profiling comparisons show that 28 genes are differentially expressed in EBS patients compared to control subjects and 41 genes in severe phenotype patients (EBS-DM) compared to their paired controls. Nine genes involved in fatty acid metabolism and two genes in epidermal keratinization are common altered expressed genes (up regulated) between the two subgroups. These two biological pathways contribute both to the formation of the cell envelope barrier and seem to be defective in the severe EBS phenotype. This study identifies, for the first time, the fatty acid metabolism disruption in EBS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • DNA Mutational Analysis*
  • Epidermolysis Bullosa Simplex / genetics*
  • Female
  • Gene Expression Profiling*
  • Humans
  • Keratin-14 / genetics*
  • Keratin-5 / genetics*
  • Lipid Metabolism
  • Male
  • Middle Aged
  • Mutation
  • Oligonucleotide Array Sequence Analysis


  • KRT14 protein, human
  • KRT5 protein, human
  • Keratin-14
  • Keratin-5